The DOI matches its Crossref record; 181 of the 194 references it cites were found in a registry or an index, and 1 are not checked yet; 22 of the 87 sources its claims cite were checked for support.
New insights into retinoid metabolism and cycling within the retina
Open accessAbstract
Review of recent findings regarding transport of retinoids, mechanisms supplying chromophore to rods and cones, and metabolism of retinoids within the posterior segment of the eye.
Verified 2026-10-05 · 1 reference not checked yet
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Written from the paper’s full text.
TL;DR
This review synthesizes evidence that retinal chromophore supply involves both the classic RPE-based visual cycle and a cone-specific cycle involving Müller cells. It also highlights unexpected findings on RPE65 localization in cones and on A2E/lipofuscin distribution that challenge older models of retinoid metabolism and retinal degeneration.
Key findings
- Two retinoid cycles are proposed: the classic visual cycle in the RPE supplies both rods and cones, while a cone-specific cycle involving Müller cells supplies cones, with DES1 proposed as an isomerase and 11-cis retinol as a cone-usable intermediate.
- RPE65 is present in cones, but its role there is not isomerization; localization varies by species and cone type—mouse cone outer segments, human red/green cone outer segments but not blue cones, and the inner-segment paraboloid in cone-dominant Anolis lizard.
- In mice, MALDI imaging showed A2E distribution correlated with lipofuscin fluorescence, with stronger correlation at older ages and in Abca4−/− mice; the oxidized A2E fraction was constant at 0.17 ± 0.03 oxygen per A2E. In human eyes, A2E did not correlate with lipofuscin and was 50–100-fold more abundant in the far periphery than in the center, independent of age.
- 11-cis retinal itself can generate lipofuscin precursors without light, challenging the view that A2E and lipofuscin arise mainly from light-generated all-trans retinal.
Methods
- Design: narrative review integrating biochemical, electrophysiological, imaging, genetic, and structural studies rather than reporting a single new experiment.
- Data/sample: cited work across species and preparations, including mouse, salamander, frog, gecko, zebrafish, chicken, lizard, and human retina/RPE, as well as mouse models such as Rpe65−/−, Lrat−/−, Nrl−/−, Irbp−/−, and Abca4−/−.
- Main analysis: thematic synthesis comparing classic and cone visual cycles, RPE65 localization and function, IRBP roles, retinoid reduction, lipofuscin/A2E formation, and therapeutic implications.
Limitations
- Stated in the paper: many mechanisms remain unclear, including the role of RPE65 in cones, details of IRBP function in cone pigment regeneration, cone opsin trafficking, why human posterior pole fluorescence lacks high A2E, and how best to model the human retina.
- Evident from the text: as a review, conclusions depend on cited studies that differ in species, mouse strain, antibodies, and methods; RPE65 detection in cones is noted as controversial because strain-dependent RPE65 levels and antibody affinity affect immunostaining.
- Evident from the text: human A2E/lipofuscin findings come from postmortem eyes, and murine models may not fully represent human retinal organization or disease.
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Claims the paper makes
21 Own interpretation · 19 No full text of the sources · 18 Sources not found · 8 Supported · 6 Supported so far · 6 Not checked yet · 6 Own result · 4 Partly supported · 2 No basis given · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“RPE65 converts all-trans retinyl-ester to 11-cis retinol (Jin et al., 2005; Moiseyev et al., 2005; Redmond et al., 2005)”
§ New insights into retinoid metabolism and cycling within the retina > 3. Retinoid processing for the rod photoreceptors > 3.1 Classic visual cycle
What the sources say
- Not checked — no full text of the sourcecites Jin et al., 2005 source
- Supportedcites Moiseyev et al., 2005 source
The paper explicitly states that RPE65 converts all-trans retinyl ester to 11-cis retinol in the Fig. 6 caption (Discussion). The Discussion also concludes that RPE65 is the enzyme responsible for this isomerohydrolase activity. (LLM, conf=0.95)
- Supportedcites Redmond et al., 2005 source
The introductory passage in our copy (labelled Abstract; page unavailable) identifies all-trans-retinyl esters as the substrate for the isomerohydrolase and 11-cis-retinol as its product. The Abstract and Discussion identify RPE65 as having a catalytic role in that reaction, in conjunction with LRAT. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
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The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“In the RPE, RPE65 is the accepted isomerohydrolase that converts all-trans retinyl-ester to 11-cis retinol (Jin et al., 2005; Moiseyev et al., 2005; Redmond et al., 2005).”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.1 Cone visual cycle
What the sources say
- Not checked — no full text of the sourcecites Jin et al., 2005 source
- Supportedcites Moiseyev et al., 2005 sourceExperimental — accuracy not yet measured
The Discussion concludes that RPE65 is the enzyme responsible for isomerohydrolase activity. The Fig. 6 model identifies all-trans retinyl ester as its substrate and 11-cis retinol as its product in the RPE visual cycle. The supplied passages do not give page numbers. (LLM, conf=0.94)
- Supportedcites Redmond et al., 2005 sourceExperimental — accuracy not yet measured
The Abstract describes conversion of all-trans-retinyl esters to 11-cis-retinol in the RPE visual cycle and identifies RPE65 as the isomerohydrolase. The Discussion concludes that RPE65 has an enzymatic role in this reaction, working with LRAT, which supplies its substrate. (LLM, conf=0.93)
boosteddirect- Asserted: passes — The authors put it forward as true.
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The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Recent evidence suggests the existence of a second retinoid visual cycle within the vertebrate retina functioning in parallel with the classic visual cycle to specifically support rapid cone pigment regeneration (Figure 5; for reviews, see (Muniz et al., 2007; Wang and Kefalov, 2011; Wolf, 2004)).”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.1 Cone visual cycle
What the sources say
- Partly supportedcites Muniz et al., 2007 sourceExperimental — accuracy not yet measured
The discussion of the cone cycle (section C, page not provided) reports evidence from cone-dominated chicken retina that it supports rapid cone pigment regeneration. But section D-3 says whether this retinal cone cycle coexists with the classic RPE cycle in duplex retinas remains to be examined; the paper does not establish parallel operation across vertebrate retinas. (LLM, conf=0.84)
- Supportedcites Wang and Kefalov, 2011 source
Section 3 describes evidence for a second, cone-specific retinoid cycle in the retina that could rapidly supply recycled chromophore. Section 6.4 reports that the retinal and classic RPE cycles work simultaneously, increasing cone sensitivity and speeding dark adaptation. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites Wolf, 2004 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In the murine RPE, we found a marked agreement between the MALDI images of A2E and the fluorescence of lipofuscin in the RPE.”
§ New insights into retinoid metabolism and cycling within the retina > 5. Products of retinoid metabolism > 5.4 Distribution of A2E in the RPE
What the sources say
- Supportedcites Grey et al., 2011 source
The Discussion states that there was “marked agreement” between A2E MALDI images and lipofuscin fluorescence in mouse RPE. It notes that the agreement was not perfect and was strongest where A2E levels were high. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Taken together, these pieces of evidence have led to the proposal that bis-retinoid precursors of lipofuscin, such as A2PE, form in the photoreceptor OS from all-trans retinal that is escaping reduction to retinol (Katz and Redmond, 2001; Katz and Robinson-Jr, 2002; Sparrow et al., 2010).”
§ New insights into retinoid metabolism and cycling within the retina > 5. Products of retinoid metabolism > 5.2 Retinoids and lipofuscin formation
What the sources say
- Not checked — no full text of the sourcecites Katz and Redmond, 2001
- Not checked — no full text of the sourcecites Katz and Robinson-Jr, 2002 source
- Supportedcites Sparrow et al., 2010 source
The section on photoreceptor origins reports A2PE formation in isolated outer segments and proposes that its biosynthesis begins there through reactions with all-trans-retinal. It also says all-trans-retinal is normally reduced to all-trans-retinol before transfer to the RPE, consistent with the proposal that retinal used to form A2PE escapes that reduction. The supplied copy gives no page number. (LLM, conf=0.91)
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In the paper
“These findings are in agreement with the data obtained from the tissue punch study (Bhosale et al., 2009), and demonstrate that lipofuscin fluorescence is not an adequate monitor of A2E in the human eye.”
§ New insights into retinoid metabolism and cycling within the retina > 5. Products of retinoid metabolism > 5.4 Distribution of A2E in the RPE
What the sources say
- Partly supportedcites Bhosale et al., 2009 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says noninvasive quantitative A2E measurements in humans are difficult to perform reliably. The tissue-punch Results (page unavailable) quantify A2E by HPLC, but the paper does not compare those measurements with lipofuscin fluorescence or establish that fluorescence is an inadequate monitor of A2E. (LLM, conf=0.78)
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In the paper
“Second, bis-retinoids constitute the major extractable component of lipofuscin (Kim et al., 2007; Sparrow et al., 2012).”
§ New insights into retinoid metabolism and cycling within the retina > 5. Products of retinoid metabolism > 5.2 Retinoids and lipofuscin formation
What the sources say
- Partly supportedcites Kim et al., 2007 sourceExperimental — accuracy not yet measured
The Discussion identifies bisretinoids as RPE lipofuscin pigments and says the all-trans-retinal dimer series is the most abundant of the lipofuscin chromophores characterized in Abcr−/− mice. It does not establish that bisretinoids constitute the major extractable component of lipofuscin generally; the abundance finding is limited to characterized chromophores in that mouse model. (LLM, conf=0.84)
- Supportedcites Sparrow et al., 2012 source
Section 2.1 states that all isolated and characterized constituents of RPE lipofuscin are bisretinoid pigments. The Conclusions likewise describe RPE lipofuscin as a mixture of bisretinoids, supporting the claim about its extractable components. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Cones in Irbp-/- mice were found to be retinoid-deficient under photopic conditions in two studies (Parker et al., 2009), leading to the proposal that 11-cis retinol supplies are disrupted in the absence of IRBP.”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.3 Role of IRBP in cone pigment regeneration
What the sources say
- Supportedcites Parker et al., 2009 source
The Results section reports that photopic ERGs were used to test for 11-cis retinal deficiency in Irbp−/− cones and that 9-cis retinal treatment restored their responses. The Discussion explicitly describes the cones as retinoid-deficient. This supports deficiency, rather than a complete absence of retinoids. (LLM, conf=0.91)
plain- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“studies regarding retinoid analogues have shown that the binding constraints of the various rod and cone opsins are quite different.”
§ New insights into retinoid metabolism and cycling within the retina > 1. Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Our recent findings that RPE65, the proposed isomerase in the RPE, is present within cones (Tang et al., 2011a; Tang et al., 2011b)”
§ New insights into retinoid metabolism and cycling within the retina > 1. Introduction
What the sources say
- Not matchedcites Tang et al., 2011a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Tang et al., 2011b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
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- Not matched
- It may state two separate claims as one. 37
- Probably not a substantial claim. 3
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Data to support this come from Lrat-/- mouse studies (Fan et al., 2008; Zhang et al., 2008), where the lack of esterification of all-trans retinol in the RPE, the substrate for RPE65-dependent isomerization (Moiseyev et al., 2003), leads to a similar degeneration of cones as observed in the Rpe65-/- mouse.”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.1 Cone visual cycle
What the sources say
- Not checked — no full text of the sourcecites Fan et al., 2008 source
- Supportedcites Zhang et al., 2008 source
The Introduction reports that Lrat−/− mice have only trace amounts of retinyl esters, consistent with a block at the esterification step. The Results section reports cone loss in both Lrat−/− and Rpe65−/− mice, with no significant difference in their overall cone populations, although regional losses differ. The substrate detail is separately cited to Moiseyev et al. in the citing sentence. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites Moiseyev et al., 2003 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Salamander cones maintained within an isolated retina free of the RPE recover light sensitivity after bleaching; however, this recovery disappears in bleached cones disassociated from the retina (Wang et al., 2009).”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.1 Cone visual cycle
What the sources say
- Supportedcites Wang et al., 2009 source
The Results section, “The Retina Promotes Cone Dark Adaptation,” reports that cones in a whole isolated salamander retina recovered sensitivity after bleaching without pigment epithelium or added chromophore. Under the same bleaching conditions, cones dissociated from the retina before bleaching showed persistent desensitization unless given exogenous chromophore. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Knocking down the expression of CRALBP in the Müller cells of zebrafish larvae by using antisense morpholinos results in a substantial decrease in 11-cis retinal and reduction in light sensitivity, supporting the key role of this protein (Collery et al., 2008; Fleisch et al., 2008).”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.1 Cone visual cycle
What the sources say
- Not checked — no full text of the sourcecites Collery et al., 2008 source
- Supportedcites Fleisch et al., 2008 source
The section on 11-cis-retinal reports that knocking down Cralbp b, the Müller-cell paralog, reduced 11-cis-retinal to about 50% of control levels. The visual-performance section reports reduced light responsiveness in Cralbp-deficient larvae, with a more pronounced effect from Müller-cell Cralbp b deficiency. (LLM, conf=0.93)
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The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Mice whose RPE65 gene has been knocked out (Rpe65-/-) do not generate 11-cis retinal (Redmond et al., 1998) and exhibit rapid cone loss and cone opsin mistrafficking (Fan et al., 2008; Tang et al., 2010; Znoiko et al., 2005).”
§ New insights into retinoid metabolism and cycling within the retina > 3. Retinoid processing for the rod photoreceptors > 3.2 Role of RPE65
What the sources say
- Not checked — no full text of the sourcecites Redmond et al., 1998 source
- Not checked — no full text of the sourcecites Fan et al., 2008 source
- Supportedcites Tang et al., 2010 source
The citation to Tang et al. supports the rapid cone loss and cone opsin mistrafficking portion of the sentence; the 11-cis retinal statement is separately cited to Redmond et al. Tang et al.’s Discussion reports significant cone loss by P30 in Rpe65−/− mice and describes disrupted trafficking of cone opsins before P30. Page numbers are not available in the supplied passages. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Interestingly, 11-cis retinol is now known to act as an agonist to rod opsin, activating the rod opsins in a light-independent manner (Kono et al., 2008).”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.1 Cone visual cycle
What the sources say
- Supportedcites Kono et al., 2008 source
The Results report that 11-cis retinol acts as an agonist of bovine rod opsin, increasing its activity sevenfold over opsin alone. The Discussion says that interaction with opsin could spuriously activate the signaling cascade in the dark, supporting the light-independent aspect of the claim. (LLM, conf=0.93)
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Subsequently, bis-retinoids enter the RPE through the daily phagocytosis of photoreceptor outer segments (Young, 1967), ending up in the lysosomal compartment where they accumulate in the form of lipofuscin.”
§ New insights into retinoid metabolism and cycling within the retina > 5. Products of retinoid metabolism > 5.2 Retinoids and lipofuscin formation
What the sources say
- Partly supportedcites Young, 1967 sourceExperimental — accuracy not yet measured
The Discussion (p. 68) places continual outer-segment renewal and removal of discs at the tip contacting the retinal pigment epithelium. It does not establish daily phagocytosis or show that bis-retinoids enter the RPE; the paper says evidence for labeled outer-segment protein in the pigment epithelium is equivocal. It also does not address lysosomal lipofuscin accumulation. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The kinetics of retinol formation, however, are faster in the cone than in the rod (Ala-Laurila et al., 2006), underlining the importance of the higher retinol dehydrogenase activity in the former.”
§ New insights into retinoid metabolism and cycling within the retina > 5. Products of retinoid metabolism > 5.1 Reduction of all-trans retinal
What the sources say
- Supportedcites Ala-Laurila et al., 2006 source
The Results report faster retinol production in salamander red- and blue-sensitive cones than in the rods compared with them. The Discussion (Retinol Clearance) identifies a faster retinol dehydrogenase (RDH) reaction in cones as one reason for their faster retinol production. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Parker et al. (Parker et al., 2009) found a reduction in cone ERG responses in Irbp-/- mice having the Met450 variant of RPE65 but observed no change in cone density or cone opsin levels and distribution.”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.3 Role of IRBP in cone pigment regeneration
What the sources say
- Supportedcites Parker et al., 2009 source
Materials and Methods (Animals; page unavailable) says the strains were genotyped to confirm the Leu450Met Rpe65 variant. The Results sections on photopic ERGs, cone density, and cone opsins (pages unavailable) report reduced cone responses in Irbp−/− mice relative to WT, similar cone densities and opsin levels, and normal opsin localization. (LLM, conf=0.94)
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The isoform of RPE65 appears to affect the phenotype of Irbp-/- mice as Jin et al. (Jin et al., 2009) reported cones in Irbp-/- mice with the Leu450 variant of RPE65 also had reduced outer segment length, partially mislocalized cone opsin, and underwent progressive degeneration.”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.3 Role of IRBP in cone pigment regeneration
What the sources say
- Supportedcites Jin et al., 2009 source
The Introduction identifies the studied Irbp−/− mice as carrying Leu450 Rpe65 and explains why Rpe65 genotype matters when interpreting their phenotype. The Discussion reports 2.2-fold shorter cone outer segments, partial M-opsin mislocalization, and reduced cone numbers rather than a developmental deficit, supporting the cited description of cone degeneration. Page numbers are not available in our copy. (LLM, conf=0.88)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Using isolated Nrl-/-Rpe65-/-retinas, IRBP was shown to deliver 11-cis retinol for oxidation in cones and to enhance the efficiency of the oxidation reaction (Parker et al., 2011).”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.3 Role of IRBP in cone pigment regeneration
What the sources say
- Supportedcites Parker et al., 2011 source
The Introduction states that oxidation assays in isolated Nrl−/−Rpe65−/− retinas showed IRBP improves the efficiency of 11-cis retinal production. The Results describe IRBP delivering 11-cis retinol to those retinas for oxidation, and the Discussion summary identifies IRBP as an effective vehicle for delivery to cones. Page numbers are not available in our copy. (LLM, conf=0.95)
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Supported
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The rates of sensitivity recovery (Perry and McNaughton, 1991) and visual pigment regeneration (Schnapf et al., 1990) are greater in cones than in rods (Baylor et al., 1979; Baylor et al., 1984).”
§ New insights into retinoid metabolism and cycling within the retina > 2. Visual pigments and chromophore binding > 2.4 Chromophore binding to visual pigments
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“In humans, RPE65 appears to be selectively expressed in the OS regions of cones that detect green/red light, but not in blue cones (Tang et al., 2011a).”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.2 RPE65 within cones
What the sources say
- Not matchedcites Tang et al., 2011a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedged- Asserted: passes — The authors put it forward as true.
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- Not matched
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In the paper
“chromophore has been demonstrated to be exchanged in the dark with cone pigments, but not rhodopsin (Crescitelli, 1984; Matsumoto et al., 1975).”
§ New insights into retinoid metabolism and cycling within the retina > 2. Visual pigments and chromophore binding > 2.4 Chromophore binding to visual pigments
What the sources say
- Not checked — no full text of the sourcecites Crescitelli, 1984 source
- Not matchedcites Matsumoto et al., 1975
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosted- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Bleached cones, but not bleached rods, were first demonstrated to regenerate resting dark current and light-sensitivity after the addition of 11-cis retinol in single salamander cell electrophysiological recordings (Jones et al., 1989).”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.1 Cone visual cycle
What the sources say
- Not checked — no full text of the sourcecites Jones et al., 1989 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Recently, the Travis group identified the presence of dihydroceramide desaturase-1 (DES1) in Müller cells and reported that this protein mediates a direct isomerization of all-trans retinol to 11-cis retinol (Kaylor et al., 2012).”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.1 Cone visual cycle
What the sources say
- Not matchedcites Kaylor et al., 2012
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We have localized RPE65 to cones although, interestingly, there does not appear to be a common location within cones for RPE65 among the cones of different species that we have studied.”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.2 RPE65 within cones
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Surprisingly, the RPE65-based complex is not specific for the 11-cis isomer, but may be driven by a mass action effect of the binding protein(s) (Redmond et al., 2010).”
§ New insights into retinoid metabolism and cycling within the retina > 3. Retinoid processing for the rod photoreceptors > 3.2 Role of RPE65
What the sources say
- Not checked — no full text of the sourcecites Redmond et al., 2010 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In vitro studies had demonstrated up to nine oxygens could be detected on A2E exposed to oxidizing conditions (Ben-Shabat et al., 2002b); however, the tissue profiling studies only detected A2E with an addition of a maximum of 3 oxygens.”
§ New insights into retinoid metabolism and cycling within the retina > 5. Products of retinoid metabolism > 5.4 Distribution of A2E in the RPE
What the sources say
- Not matchedcites Ben-Shabat et al., 2002b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There is growing evidence to show that two separate retinoid cycles exist, one that supplies both rods and cones with chromophore (classic visual cycle) and another that specifically supplies cones (cone visual cycle), possibly as a supplemental source.”
§ New insights into retinoid metabolism and cycling within the retina > 1. Introduction
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“the unexpected distribution of the retinoid metabolite N-retinylidene-N-retinylethanolamine (A2E) ((Ablonczy et al., 2012a) and see Fig. 12) in the human RPE pose challenges to previously accepted mechanisms.”
§ New insights into retinoid metabolism and cycling within the retina > 1. Introduction
What the sources say
- Not matchedcites Ablonczy et al., 2012a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Unlike in the RPE, the role of RPE65 in cones remains unclear.”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.2 RPE65 within cones
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Using suction electrodes to mask the OS of isolated salamander rods and cones, 11-cis retinal presented to the cell bodies of bleached photoreceptors restored light sensitivity in cones, but had no effect on rods (Jin et al., 1994).”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.1 Cone visual cycle
What the sources say
- Not checked — no full text of the sourcecites Jin et al., 1994 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This last finding is likely the basis of some controversy over the presence of RPE65 in cones (summarized in (Tang et al., 2011b)) as RPE65 is highest in the C57BL/6 mice (low levels of RPE65 in the RPE) and undetectable by immunostaining in BALB/c and 129Sv mouse eyecups where RPE65 is high in the RPE.”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.2 RPE65 within cones
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It has been shown that cones are capable of carrying out 11-cis retinol oxidation, whereas rods cannot.”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.1 Cone visual cycle
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Its involvement in promoting the cone visual cycle is supported by evidence that IRBP binds 11-cis retinol endogenously (Saari et al., 1985), is co-localized with Müller cell processes surrounding the cone cell body (Uehara et al., 1990), and is found in high concentrations around the cones (Carter-Dawson and Burroughs, 1992a, 1992b).”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.3 Role of IRBP in cone pigment regeneration
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, Müller cells are capable of converting all-trans retinol to 11-cis retinol similar to what is observed in the RPE with the exception of the final oxidation reaction to generate 11-cis retinal.”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.1 Cone visual cycle
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This may be due to a requirement of green and red cones for a supplemental source of retinoids for rapid chromophore turnover, as they are the only subtypes that appear within the fovea.”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.2 RPE65 within cones
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By not performing the final oxidation step in the Müller cells, 11-cis retinol becomes a source of chromophore usable only by cones.”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.1 Cone visual cycle
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We thus propose that RPE65 is acting as a retinol binding protein, and the distribution within the cones of various species may vary depending on the localization of the hydrolysis/oxidation reactions.”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.2 RPE65 within cones
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both rods and cones apparently receive 11-cis retinal from the RPE, and we are referring to this as the classic visual cycle to distinguish it from a more recently identified cone visual cycle involving the Müller cells that appears to be exclusive to cones”
§ New insights into retinoid metabolism and cycling within the retina > 3. Retinoid processing for the rod photoreceptors > 3.1 Classic visual cycle
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A cone-specific visual cycle involving the Müller cells (Kaylor et al., 2012) has been proposed and an isomerase identified which is localized in Müller cells.”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.1 Cone visual cycle
What the sources say
- Not matchedcites Kaylor et al., 2012
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Third, lipofuscin accumulation requires the phagocytosis of the photoreceptor OS by the RPE, and in the absence of phagocytosis, retinoid-derived fluorescent material accumulates in the photoreceptors (Katz et al., 1987).”
§ New insights into retinoid metabolism and cycling within the retina > 5. Products of retinoid metabolism > 5.2 Retinoids and lipofuscin formation
What the sources say
- Not checked — no full text of the sourcecites Katz et al., 1987 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Finally, all-trans retinal can form A2PE in rod OS membranes. This includes the formation of A2PE from all-trans retinal added exogenously to membranes (Liu et al., 2000), as well as from retinal released endogenously from rhodopsin following bleaching (Ben-Shabat et al., 2002b).”
§ New insights into retinoid metabolism and cycling within the retina > 5. Products of retinoid metabolism > 5.2 Retinoids and lipofuscin formation
What the sources say
- Not checked — no full text of the sourcecites Liu et al., 2000 source
- Not matchedcites Ben-Shabat et al., 2002b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“First, lipofuscin levels are greatly decreased in mice that lack RPE65 (Katz and Redmond, 2001), indicating that lipofuscin formation requires the generation of 11-cis retinal.”
§ New insights into retinoid metabolism and cycling within the retina > 5. Products of retinoid metabolism > 5.2 Retinoids and lipofuscin formation
What the sources say
- Not matchedcites Katz and Redmond, 2001
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The lack of correlation between A2E and lipofuscin in the human eye clearly shows that further study is needed.”
§ New insights into retinoid metabolism and cycling within the retina > 7. Conclusions and Future Directions
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“As IRBP protects the isomeric state of 11-cis retinol, even in the presence of light (Crouch et al., 1992), the protein is likely to have a critical role in the delivery of 11-cis retinol to cones and to facilitate cone function.”
§ New insights into retinoid metabolism and cycling within the retina > 4. Retinoid processing for the cone photoreceptors > 4.3 Role of IRBP in cone pigment regeneration
What the sources say
- Not checked — no full text of the sourcecites Crouch et al., 1992 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It would allow cone photoreceptors to recycle the chromophore faster than rods, so they can support faster visual pigment regeneration.”
§ New insights into retinoid metabolism and cycling within the retina > 5. Products of retinoid metabolism > 5.1 Reduction of all-trans retinal
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This is in agreement with the faster release of retinal from the photoactivated visual pigment, and the higher retinol dehydrogenase activity in cones (Miyazono et al., 2008).”
§ New insights into retinoid metabolism and cycling within the retina > 5. Products of retinoid metabolism > 5.1 Reduction of all-trans retinal
What the sources say
- Not checked — no full text of the sourcecites Miyazono et al., 2008 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
No evidence exists for RPE65 within Müller cells.
“There is no evidence for the presence of RPE65 within Müller cells”
The authors state this as an assumption.
When light is present, the all-trans retinal formed by light absorption is taken to be converted to all-trans retinol and moved to the RPE for ester storage.
“Under light conditions, the all-trans retinal produced from the absorption of light is assumed to be reduced to all-trans retinol and then transported to the RPE where it is stored as the ester.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“The photosensitive active retinoid, 11-cis-retinal, is produced in the RPE and delivered to the photoreceptors.”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [69]
The cited source says what the claim attributes to it.
In the citing paper
“the RPE expresses key metabolic enzymes required for production of the visual chromophore, 11-cis-retinal, and thus comprises an integral part of the retinoid cycle.”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [69]
The cited source says what the claim attributes to it.
In the citing paper
“Several potentially toxic byproducts are condensation compounds derived from all-trans-retinal.”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [69]
In the citing paper
“OS phagocytosis also allows for recycling of docosahexaenoic acid (DHA) (Gordon and Bazan, 1990; Rodriguez de Turco et al., 1991) and visual pigment to photoreceptors to maintain visual function (Tang et al., 2013).”
From Microtubule-associated protein 1 light chain 3B, (LC3B) is necessary to maintain lipid-mediated homeostasis in the retinal pigment epithelium (2018) · cites this paper as Tang et al., 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ New insights into retinoid metabolism and cycling within the retina > 5. Products of retinoid metabolism > 5.2 Retinoids and lipofuscin formation
“mice that lack retinol dehydrogenases, the enzymes that oxidize all-trans retinol to retinal show increased A2E accumulation in the RPE”
§ New insights into retinoid metabolism and cycling within the retina > 3. Retinoid processing for the rod photoreceptors > 3.1 Classic visual cycle
“all-trans retinal is released from opsin and reduced to all-trans retinol by the combined action of RDH8 and RDH12”
Citations
Cites
Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis
Maguire, A. M., Simonelli, F., Pierce, E. A., Pugh, E. N., Mingozzi, F., Bennicelli, J., Banfi, S., Marshall, K. A., Testa, F., Surace, E. M., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802315 · Cited by 2,145 · cited 1×
“Gene therapy studies on mouse (Pang et al., 2006) and canine (Acland et al., 2001, 2005) models, as well as LCA2 patients (Bainbridge et al., 2008; Maguire et al., 2008, 2009), have shown that inserting a functional gene for RPE65 into RPE cells holds great promise for restoring visual function.”
Effect of gene therapy on visual function in Leber’s congenital amaurosis
Bainbridge, J. W. B., Smith, A. J., Barker, S. S., Robbie, S., Henderson, R., Balaggan, K., Viswanathan, A., Holder, G. E., Stockman, A., Tyler, N., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802268 · Cited by 1,924 · cited 2×
“, 2001, 2005) models, as well as LCA2 patients (Bainbridge et al., 2008; Maguire et al., 2008, 2009), have shown that inserting a functional gene for RPE65 into RPE cells holds great promise for restoring visual function.”
Gene therapy restores vision in a canine model of childhood blindness
Acland, G. M., Aguirre, G. D., Ray, J., Zhang, Q., Aleman, T. S., Cideciyan, A. V., Pearce-Kelling, S. E., Anand, V., Zeng, Y., Maguire, A. M., et al. (2001) · Nature Genetics · doi:10.1038/ng0501-92 · Cited by 1,202 · cited 1×
“Gene therapy studies on mouse (Pang et al., 2006) and canine (Acland et al., 2001, 2005) models, as well as LCA2 patients (Bainbridge et al., 2008; Maguire et al., 2008, 2009), have shown that inserting a functional gene for RPE65 into RPE cells holds great promise for restoring visual function.”
The renewal of photoreceptor cell outer segments
Young, R. W. (1967) · The Journal of Cell Biology · doi:10.1083/jcb.33.1.61 · Cited by 1,184 · cited 1×
“Subsequently, bis-retinoids enter the RPE through the daily phagocytosis of photoreceptor outer segments (Young, 1967), ending up in the lysosomal compartmentwhere they accumulate in the form of lipofuscin.”
Chemistry and metabolism of lipids in the vertebrate retina
Fliesler, A. J., & Anderson, R. E. (1983) · Progress in Lipid Research · doi:10.1016/0163-7827(83)90004-8 · Cited by 1,052 · cited 1×
“All-trans retinal can form a Schiff base with amine groups, including the one on phosphatidylethanolamine, a major lipid component of OS membranes (Fliesler and Anderson, 1983).”
Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle
Redmond., T. M., Yu, S., Lee, E., Bok, D., Hamasaki, D., Chen, N., Goletz, P., Ma, J.-X., Crouch, R. K., & Pfeifer, K. (1998) · Nature Genetics · doi:10.1038/3813 · Cited by 929 · cited 3×
“Mice whose RPE65 gene has been knocked out (Rpe65 / ) do not generate 11-cis retinal (Redmond et al., 1998) and exhibit rapid cone loss and cone opsin”
Self-citationNrl is required for rod photoreceptor development
Mears, A. J., Kondo, M., Swain, P. K., Takada, Y., Bush, R. A., Saunders, T. L., Sieving, P. A., & Swaroop, A. (2001) · Nature Genetics · doi:10.1038/ng774 · Cited by 912 · cited 2×
“, 2007), a model for a pure-cone retina (Mears et al., 2001).”
Maguire, A. M., High, K. A., Auricchio, A., Wright, J. F., Pierce, E. A., Testa, F., Mingozzi, F., Bennicelli, J. L., Ying, G.-S., Rossi, S., et al. (2009) · The Lancet · doi:10.1016/s0140-6736(09)61836-5 · Cited by 865
A Membrane Receptor for Retinol Binding Protein Mediates Cellular Uptake of Vitamin A
Kawaguchi, R., Yu, J., Honda, J., Hu, J., Whitelegge, J., Ping, P., Wiita, P., Bok, D., & Sun, H. (2007) · Science · doi:10.1126/science.1136244 · Cited by 836 · cited 1×
“STRA6, the recently identified membrane receptor for plasma retinol binding protein (RPB), mediates the cellular uptake of trans retinol into the RPE (Kawaguchi et al., 2007; Sun, 2012).”
Rods and cones in the mouse retina. I. Structural analysis using light and electron microscopy
Carter‐Dawson, L. D., & LaVail, M. M. (1979) · The Journal of Comparative Neurology · doi:10.1002/cne.901880204 · Cited by 695 · cited 1×
“In rod-dominant retinas such as in mice and humans, rods comprise over 94% of the total photoreceptor population (Carter-Dawson and LaVail,1979).”
The photocurrent, noise and spectral sensitivity of rods of the monkey Macaca fascicularis.
Baylor, D. A., Nunn, B. J., & Schnapf, J. L. (1984) · The Journal of Physiology · doi:10.1113/jphysiol.1984.sp015518 · Cited by 690 · cited 1×
“The rates of sensitivity recovery (Perry and McNaughton, 1991) and visual pigment regeneration (Schnapf et al., 1990) are greater in cones than in rods (Baylor et al., 1979, 1984).”
Mutations in RPE65 cause Leber's congenital amaurosis
Marlhens, F., Bareil, C., Griffoin, J.-M., Zrenner, E., Amalric, P., Eliaou, C., Liu, S.-Y., Harris, E., Redmond, T. M., Arnaud, B., et al. (1997) · Nature Genetics · doi:10.1038/ng1097-139 · Cited by 606 · cited 1×
“Mutations to RPE65 are associated with Type 2 Leber congenital amaurosis (LCA2), an early onset congenital blindness that reduces or abolishes the innate synthesis of 11-cis retinal (Harris, 2001; Marlhens et al., 1997).”
Molecular evolution of vertebrate visual pigments
Yokoyama, S. (2000) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(00)00002-1 · Cited by 588 · cited 1×
“Phylogenetic analyses of opsin sequences demonstrate that opsins can be divided into 5 classes correlating roughly with absorption properties (Ebrey and Koutalos, 2001; Yokoyama, 2000).”
Applebury, M. L., Antoch, M. P., Baxter, L. C., Chun, L. L. Y., Falk, J. D., Farhangfar, F., Kage, K., Krzystolik, M. G., Lyass, L., & Robbins, J. T. (2000) · Neuron · doi:10.1016/s0896-6273(00)00062-3 · Cited by 566 · cited 2×
“…studies have shown that several species of rodents, notably thewell characterized and genetically-modified mouse, contain a mixture of the two cone opsins with a well-defined dorsal-ventral gradient across the retina, even in the wild-type animals (Applebury et al., 2000; Lukáts et al., 2005).”
RPE65 is the isomerohydrolase in the retinoid visual cycle
Moiseyev, G., Chen, Y., Takahashi, Y., Wu, B. X., & Ma, J.-X. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503460102 · Cited by 536 · cited 5×
“…concluded that RPE65 was the isomerohydrolase, most probably acting in complex with other retinyl-binding protein(s) and dehydrogenase(s), responsible for converting all-trans retinyl-ester to 11-cis retinol within the RPE (Jin et al., 2005; Moiseyev et al., 2005; Redmond et al., 2005).”
InfluentialRetinal age pigments generated by self-assembling lysosomotropic detergents
Eldred, G., & Lasky, M. R. (1993) · Nature · doi:10.1038/361724a0 · Cited by 489 · cited 2×
“, 2010), but the best-studied bis-retinoid is still A2E (Eldred and Lasky, 1993; Parish et al., 1998; Sakai et al., 1995).”
The membrane current of single rod outer segments
Baylor, D. A., Lamb, T. D., & Yau, K. (1979) · Vision Research · doi:10.1016/0042-6989(79)90077-4 · Cited by 486
Visual transduction in cones of the monkey Macaca fascicularis.
Schnapf, J. L., Nunn, B. J., Meister, M., & Baylor, D. A. (1990) · The Journal of Physiology · doi:10.1113/jphysiol.1990.sp018193 · Cited by 478 · cited 2×
“The rates of sensitivity recovery (Perry and McNaughton, 1991) and visual pigment regeneration (Schnapf et al., 1990) are greater in cones than in rods (Baylor et al., 1979, 1984).”
Acland, G. M., Aguirre, G. K., Bennett, J., Alemán, T. S., Cideciyan, A. V., Bennicelli, J. L., Dejneka, N. S., Pearce-Kelling, S. E., Maguire, A. M., Palczewski, K., et al. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.08.008 · Cited by 478 · cited 1×
“Gene therapy studies on mouse (Pang et al., 2006) and canine (Acland et al., 2001, 2005) models, as well as LCA2 patients (Bainbridge et al., 2008; Maguire et al., 2008, 2009), have shown that inserting a functional gene for RPE65 into RPE cells holds great promise for restoring visual function.”
Parish, C. A., Hashimoto, M., Nakanishi, K., Dillon, J., & Sparrow, J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14609 · Cited by 474 · cited 2×
“, 2010), but the best-studied bis-retinoid is still A2E (Eldred and Lasky, 1993; Parish et al., 1998; Sakai et al., 1995).”
Mata, N. L., Weng, J., & Travis, G. H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.130110497 · Cited by 456 · cited 5×
“This information is directly comparable to fluorescence measurements; therefore, the spatial distributions of individual molecular ions (such as A2E, its oxides, precursors, and degradation products) can be determined and correlated with the measured fluorescence.”
InfluentialImmunocytochemical localization of two retinoid-binding proteins in vertebrate retina.
Bunt-Milam, A. H., & Saari, J. C. (1983) · The Journal of cell biology · doi:10.1083/jcb.97.3.703 · Cited by 455 · cited 1×
“Müller cells contain CRBP and CRALBP, both of which are retinoid binding proteins found in the RPE, with the latter preferentially binding 11-cis retinoids (Bunt-Milam and Saari, 1983; Eisenfeld et al., 1985).”
Filling the Gap in Vitamin A Research
von Lintig, J., & Vogt, K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.16.11915 · Cited by 449 · cited 1×
“After b-carotene is absorbed by the intestinal lumen, it is symmetrically cleaved by b,b-carotene 15,150-monooxygenase into two molecules of all-trans retinal and eventually reduced to all-trans retinol by retinoid dehydrogenases (RDHs) (Redmond et al., 2001; von-Lintig and Vogt, 2000).”
Ebrey, T. G., & Koutalos, Y. (2001) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(00)00014-8 · Cited by 441 · cited 1×
“Phylogenetic analyses of opsin sequences demonstrate that opsins can be divided into 5 classes correlating roughly with absorption properties (Ebrey and Koutalos, 2001; Yokoyama, 2000).”
Self-citationFundus autofluorescence and development of geographic atrophy in age-related macular degeneration.
Holz, F. G., Bellman, C., STAUDT, S., Schütt, F., & Völcher, H. E. (2002) · American Journal of Ophthalmology · doi:10.1016/s0002-9394(01)01394-0 · Cited by 426 · cited 1×
“Through interaction with blue light, lipofuscin was proposed to contribute to the development of age-related macular degeneration (Birnbach et al., 1994; Holz et al., 2001; Roberts et al., 2002).”
Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium
Jin, M., Li, S., Moghrabi, W. N., Sun, H., & Travis, G. H. (2005) · Cell · doi:10.1016/j.cell.2005.06.042 · Cited by 424 · cited 5×
“…concluded that RPE65 was the isomerohydrolase, most probably acting in complex with other retinyl-binding protein(s) and dehydrogenase(s), responsible for converting all-trans retinyl-ester to 11-cis retinol within the RPE (Jin et al., 2005; Moiseyev et al., 2005; Redmond et al., 2005).”
InfluentialDiseases Caused by Defects in the Visual Cycle: Retinoids as Potential Therapeutic Agents
Travis, G. H., Golczak, M., Moise, A. R., & Palczewski, K. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.47.120505.105225 · Cited by 419 · cited 2×
“Diseases resulting in visual impairment arising from the disrupting retinoid metabolism have been recognized for some years and excellent reviews cover this area (Travis et al., 2007).”
Redmond, T. M., Poliakov, E., Yu, S., Tsai, J.-Y., Lu, Z., & Gentleman, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504167102 · Cited by 409 · cited 5×
“…concluded that RPE65 was the isomerohydrolase, most probably acting in complex with other retinyl-binding protein(s) and dehydrogenase(s), responsible for converting all-trans retinyl-ester to 11-cis retinol within the RPE (Jin et al., 2005; Moiseyev et al., 2005; Redmond et al., 2005).”
InfluentialThe topography and age relationship of lipofuscin concentration in the retinal pigment epithelium.
Wing, G. L., Blanchard, G. C., & Weiter, J. J. (1978) · PubMed · Cited by 394
The bisretinoids of retinal pigment epithelium
Sparrow, J. R., Gregory-Roberts, E., Yamamoto, K., Blonska, A., Ghosh, S. K., Ueda, K., & Zhou, J. (2012) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2011.12.001 · Cited by 392 · cited 1×
“Second, bis-retinoids constitute the major extractable component of lipofuscin (Kim et al., 2007; Sparrow et al., 2012).”
Feeney, L. (1978) · PubMed · Cited by 389
Batten, M. L., Imanishi, Y., Maeda, T., Tu, D. C., Moise, A. R., Bronson, D., Possin, D., Van Gelder, R. N., Baehr, W., & Palczewski, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312410200 · Cited by 368 · cited 2×
“Unlike the LRAT-dependent retinol esterification in the RPE, microsomes of chicken retina generated 11-cis retinyl-ester from all-trans retinol through a mechanism requiring palm-CoA as an acyl donor, suggesting this isomerase is dependent on acyl CoA-retinol acyltransferase (ARAT) (Muniz et al., 2009).”
Tan, E., Ding, X.-Q., Saadi, A., Agarwal, N., Naash, M. I., & Al-Ubaidi, M. R. (2004) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.03-1114 · Cited by 345 · cited 2×
“The cone-derived 661W cells (Tan et al., 2004) are known to have retinol esterase activity (Kanan et al.”
The membrane current of single rod outer segments
Baylor, D. A., Lamb, T. D., & Yau, K. W. (1979) · The Journal of Physiology · doi:10.1113/jphysiol.1979.sp012715 · Cited by 341 · cited 1×
“The rates of sensitivity recovery (Perry and McNaughton, 1991) and visual pigment regeneration (Schnapf et al., 1990) are greater in cones than in rods (Baylor et al., 1979, 1984).”
The Cone-specific visual cycle
Wang, J.-S., & Kefalov, V. J. (2011) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2010.11.001 · Cited by 335 · cited 2×
“5; for reviews, see Muniz et al., 2007; Wang and Kefalov, 2011; Wolf, 2004).”
Hamel, C., Tsilou, E. T., Pfeffer, B. A., Hooks, J. J., Detrick, B., & Redmond, T. M. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82319-5 · Cited by 334 · cited 3×
“RPE65 has been well-documented to be abundant in the RPE of many species (Hamel et al., 1993; Tsilou et al., 1997) and was originally proposed to be specific to that tissue.”
Wald, G., Brown, P. K., & Smith, P. H. (1955) · The Journal of General Physiology · doi:10.1085/jgp.38.5.623 · Cited by 324
Phototransduction in mouse rods and cones
Fu, Y., & Yau, K. (2007) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-006-0194-y · Cited by 310
Arikawa, K., Molday, L. L., Molday, R. S., & Williams, D. S. (1992) · The Journal of Cell Biology · doi:10.1083/jcb.116.3.659 · Cited by 308 · cited 1×
“The majority of the rod phototransduction proteins are associated with disc membranes isolated within the OS, whereas cone phototransductionproteins are embedded in theOSplasmamembrane that is arranged into stacked invaginations (Arikawa et al.,1992).”
CAROTENOIDS AND THE VISUAL CYCLE
Wald, G. (1935) · The Journal of General Physiology · doi:10.1085/jgp.19.2.351 · Cited by 302 · cited 1×
“1 for retinoid structures) as its chromophore (Wald, 1935, 1951).”
Identification, Expression, and Substrate Specificity of a Mammalian β-Carotene 15,15′-Dioxygenase
Redmond, T. M., Gentleman, S., Duncan, T. E., Yu, S., Wiggert, B. O., Gantt, E., & Cunningham, F. X. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009030200 · Cited by 279 · cited 2×
“After b-carotene is absorbed by the intestinal lumen, it is symmetrically cleaved by b,b-carotene 15,150-monooxygenase into two molecules of all-trans retinal and eventually reduced to all-trans retinol by retinoid dehydrogenases (RDHs) (Redmond et al., 2001; von-Lintig and Vogt, 2000).”
The membrane current of single rod outer segments.
Baylor, D. A., Lamb, T. D., & Yau, K. (1979) · PubMed Central · Cited by 277
Structure of cone photoreceptors
Mustafi, D., Engel, A. H., & Palczewski, K. (2009) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.05.003 · Cited by 275 · cited 1×
“2; for review, see Mustafi et al., 2009) and make synaptic associations with secondary neurons such as bipolar cells in the outer plexiform layer (OPL).”
Liu, J., Itagaki, Y., Ben-Shabat, S., Nakanishi, K., & Sparrow, J. R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m910191199 · Cited by 255 · cited 6×
“Finally, all-trans retinal can form A2PE in rod OS membranes.”
InfluentialInvolvement of All-trans-retinal in Acute Light-induced Retinopathy of Mice
Maeda, A., Maeda, T., Golczak, M., Chou, S., Desai, A., Hoppel, C. L., Matsuyama, S., & Palczewski, K. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900322200 · Cited by 248 · cited 2×
“On the other hand, a detoxifying role for A2E itself has also been suggested as it removes the highly toxic free all-trans retinal (Maeda et al., 2011, 2009a; Roberts et al., 2002).”
In vivo measurement of lipofuscin in Stargardt's disease--Fundus flavimaculatus.
Delori, F. C., Staurenghi, G., Arend, O., Dorey, C. K., Goger, D. G., & Weiter, J. J. (1995) · PubMed · Cited by 245
Jones, G. J., Crouch, R. K., Wiggert, B., Cornwall, M. C., & Chader, G. J. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.23.9606 · Cited by 244 · cited 2×
“In vitrodata from several laboratories have shown that IRBP facilitates clearance of all-trans retinol from photoreceptor cells and uptake of 11-cis retinal from the RPE (Edwards and Adler, 2000; Jones et al., 1989).”
Self-citationFundus autofluorescence and development of geographic atrophy in age-related macular degeneration.
Holz, F. G., Bellman, C., STAUDT, S., Schütt, F., & Völcker, H. E. (2001) · PubMed · Cited by 242
Visual pigment: G-protein-coupled receptor for light signals
Shichida, Y., & Imai, H. (1998) · Cellular and Molecular Life Sciences (CMLS) · doi:10.1007/s000180050256 · Cited by 242 · cited 1×
“Rod and cone opsins are members of the super-family of G-protein-coupled receptors (Shichida and Imai, 1998).”
Evolution and spectral tuning of visual pigments in birds and mammals
Hunt, D. M., Carvalho, L. S., Cowing, J. A., & Davies, W. L. (2009) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2009.0044 · Cited by 234 · cited 2×
“Recent in vitro studies of retinal release from cone opsins after bleaching compared to rhodopsin have shown that cone pigments release retinal at a much faster rate (M.H. Chen et al., 2012; Das et al., 2004; Hunt et al., 2009).”
Response properties of cones from the retina of the tiger salamander
Perry, R. J., & McNaughton, P. A. (1991) · The Journal of Physiology · doi:10.1113/jphysiol.1991.sp018444 · Cited by 216 · cited 2×
“The rates of sensitivity recovery (Perry and McNaughton, 1991) and visual pigment regeneration (Schnapf et al., 1990) are greater in cones than in rods (Baylor et al., 1979, 1984).”
Biosynthetic Studies of A2E, a Major Fluorophore of Retinal Pigment Epithelial Lipofuscin
Ben-Shabat, S., Parish, C. A., Vollmer, H. R., Itagaki, Y., Fishkin, N., Nakanishi, K., & Sparrow, J. R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m108981200 · Cited by 214 · cited 7×
“In vitro studies had demonstrated up to nine oxygens could be detected on A2E exposed to oxidizing conditions (Ben-Shabat et al., 2002b); however, the tissue profiling studies only detected A2E with an addition of a maximum of 3 oxygens.”
InfluentialHistopathology and immunocytochemistry of the neurosensory retina in fundus flavimaculatus.
Birnbach, C., Järveläínen, M., Possin, D., & Milam, A. (1994) · Ophthalmology (Rochester, Minn.) · doi:10.1016/s0161-6420(13)31725-4 · Cited by 212 · cited 1×
“Through interaction with blue light, lipofuscin was proposed to contribute to the development of age-related macular degeneration (Birnbach et al., 1994; Holz et al., 2001; Roberts et al., 2002).”
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Pang, J., Chang, B., Kumar, A., Nusinowitz, S., Noorwez, S. M., Li, J., Rani, A., Foster, T. C., Chiodo, V. A., Doyle, T. J., et al. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.09.001 · Cited by 199 · cited 2×
“Gene therapy studies on mouse (Pang et al., 2006) and canine (Acland et al., 2001, 2005) models, as well as LCA2 patients (Bainbridge et al., 2008; Maguire et al., 2008, 2009), have shown that inserting a functional gene for RPE65 into RPE cells holds great promise for restoring visual function.”
Phospholipid meets all-trans-retinal: the making of RPE bisretinoids
Sparrow, J. R., Wu, Y., Kim, C. Y., & Zhou, J. (2010) · Journal of Lipid Research · doi:10.1194/jlr.r000687 · Cited by 193
Light‐induced Damage to the Retina: Role of Rhodopsin Chromophore Revisited
Różanowska, M., & Sarna, T. (2005) · Photochemistry and Photobiology · doi:10.1562/2004-11-13-ir-371 · Cited by 183 · cited 1×
“Retinal is a reactive aldehyde and a photosensitizer (Delmelle, 1978; Krasnovsky and Kagan, 1979; Matsumoto et al., 1975; Rozanowska and Sarna, 2005), and its toxicity may play a role in several diseases of the retina.”
The visual pigment basis for cone polymorphism in the guppy, Poecilia reticulata
Archer, S., & LYTHGOE, J. N. (1990) · Vision Research · doi:10.1016/0042-6989(90)90038-m · Cited by 168 · cited 1×
“This was first shown for the guppy (Archer and Lythgoe, 1990) and the salamander (Makino and Dodd, 1996).”
Retinal Pigment Epithelium Lipofuscin Proteomics
Ng, K.-P., Gugiu, B., Renganathan, K., Davies, M. W., Gu, X., Crabb, J. S., Kim, S. R., Różanowska, M. B., Bonilha, V. L., Rayborn, M. E., et al. (2008) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m700525-mcp200 · Cited by 162
Role of photoreceptor-specific retinol dehydrogenase in the retinoid cycle in vivo
Maeda, A., Maeda, T., Imanishi, Y., Kuksa, V., Alekseev, A., Bronson, J. D., Zhang, H., Zhu, L., Sun, W., Saperstein, D. A., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501757200 · Cited by 159 · cited 1×
“Consistent with this notion, mice that lack retinol dehydrogenases, the enzymes that oxidize all-trans retinol to retinal show increased A2E accumulation in the RPE (Chrispell et al., 2009; Maeda et al., 2005).”
Crystal structure of native RPE65, the retinoid isomerase of the visual cycle
Kiser, P. D., Golczak, M., Lodowski, D. T., Chance, M. R., & Palczewski, K. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906600106 · Cited by 158 · cited 3×
“A crystal structure for RPE65 has been determined at 2.14 A resolution (Kiser et al., 2009).”
InfluentialPalczewski, K., Hooser, J. P. V., Garwin, G. G., Chen, J., Liou, G. I., & Saari, J. C. (1999) · Biochemistry · doi:10.1021/bi990504d · Cited by 157 · cited 2×
“…affect recovery of sensitivity by the rods as might have been expected if IRBP were critical for the transport of 11-cis retinal to photoreceptors (Palczewski et al., 1999; Ripps et al., 2000); however, Irbp / mice do exhibit rod degeneration (Liou et al., 1998), indicating that IRBP’s absence is…”
Intra-retinal visual cycle required for rapid and complete cone dark adaptation
Wang, J.-S., Estevez, M. E., Cornwall, M. C., & Kefalov, V. J. (2009) · Nature Neuroscience · doi:10.1038/nn.2258 · Cited by 151 · cited 4×
“This finding is particularly interesting considering the topology of Müller cell processes, as they make numerous associations with cones at this region (Sarantis and Mobbs, 1992; Wang et al., 2009).”
InfluentialPepperberg, D. R., Okajima, T.-I. L., Wiggert, B., Ripps, H., Crouch, R. K., & Chader, G. J. (1993) · Molecular Neurobiology · doi:10.1007/bf02780609 · Cited by 149
Self-citationZnoiko, S. L., Rohrer, B., Lu, K., Lohr, H. R., Crouch, R. K., & Ma, J.-X. (2005) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.04-0653 · Cited by 146 · cited 2×
“Mice whose RPE65 gene has been knocked out (Rpe65 / ) do not generate 11-cis retinal (Redmond et al., 1998) and exhibit rapid cone loss and cone opsin mistrafficking (Fan et al., 2008; Tang et al., 2010; Znoiko et al., 2005).”
Self-citationKim, S. R., Jang, Y. P., Jockusch, S., Fishkin, N. E., Turro, N. J., & Sparrow, J. R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708714104 · Cited by 145 · cited 1×
“Second, bis-retinoids constitute the major extractable component of lipofuscin (Kim et al., 2007; Sparrow et al., 2012).”
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Muller cells of chicken retina synthesize 11- cis -retinol
Das, S. R., Bhardwaj, N., Kjeldbye, H., & Gouras, P. (1992) · Biochemical Journal · doi:10.1042/bj2850907 · Cited by 135 · cited 1×
“Cultured chicken Müller cells were shown to convert all-trans retinol to alltrans and 11-cis palmitates and 11-cis retinol, similar to reactions in the classical visual cycle of the RPE (Das et al., 1992).”
Primary amines protect against retinal degeneration in mouse models of retinopathies
Maeda, A., Golczak, M., Chen, Y., Okano, K., Kohno, H., Shiose, S., Ishikawa, K., Harte, W., Palczewska, G., Maeda, T., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.759 · Cited by 135 · cited 2×
“On the other hand, a detoxifying role for A2E itself has also been suggested as it removes the highly toxic free all-trans retinal (Maeda et al., 2011, 2009a; Roberts et al., 2002).”
Boyer, N. P., Higbee, D., Currin, M. B., Blakeley, L. R., Chen, C., Ablonczy, Z., Crouch, R. K., & Koutalos, Y. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.329235 · Cited by 133 · cited 1×
“A2E formation from 11-cis retinal While it is clear that retinoids are involved in lipofuscin, recent evidence shows 11-cis retinal itself may be a major source of lipofuscin andA2E (Boyer et al., 2012).”
Self-citationRole of visual pigment properties in rod and cone phototransduction
Kefalov, V. J., Fu, Y., Marsh‐Armstrong, N., & Yau, K. (2003) · Nature · doi:10.1038/nature01992 · Cited by 133 · cited 2×
“From studies where the human rod RH1 pigment has been expressed in Xenopus M/L cones, and the human or salamander M/L cone pigment has been expressed in Xenopus rods, it has been clearly demonstrated that the respective cells have the same amplification and kinetics with either the rod or the cone opsin, thus eliminat…”
Cone Opsin Mislocalization in Rpe65−/−Mice: A Defect That Can Be Corrected by 11-cis Retinal
Rohrer, B., Lohr, H. R., Humphries, P., Redmond, T. M., Seeliger, M. W., & Crouch, R. K. (2005) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.05-0533 · Cited by 133 · cited 2×
“Furthermore, successful use of small molecules and retinoid derivatives to ameliorate the cone degeneration reported in animal models of LCA2 has been reported (Maeda et al., 2009b; Rohrer et al., 2005).”
Self-citationKatz, M. L., & Robison, W. G. (2002) · Archives of Gerontology and Geriatrics · doi:10.1016/s0167-4943(02)00005-5 · Cited by 122 · cited 5×
“…removal of all-trans retinal that occurs as a part of the light detection process is thought to be associated with the formation of lipofuscin (Katz and Redmond, 2001; Katz and Robinson, 2002; Sparrow et al., 2010), the fluorescent pigment that accumulates with age in the RPE lysosomal compartment.”
InfluentialProperties of an interphotoreceptor retinoid-binding protein from bovine retina
Saari, J. C., Teller, D. C., Crabb, J. W., & Bredberg, L. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)89715-0 · Cited by 120 · cited 2×
“Its involvement in promoting the cone visual cycle is supported byevidence that IRBP binds 11-cis retinol endogenously (Saari et al., 1985), is co-localized with Müller cell processes surrounding the cone cell body (Uehara et al.”
Retinyl Esters Are the Substrate for Isomerohydrolase
Moiseyev, G., Crouch, R. K., Goletz, P., Oatis, Redmond, T. M., & Ma, J.-X. (2003) · Biochemistry · doi:10.1021/bi026911y · Cited by 116 · cited 3×
“This retinyl-ester is the substrate for the proposed isomerohydrolase, RPE65 (Moiseyev et al., 2003).”
InfluentialSelf-citationLiou, G. I., Fei, Y., Peachey, N. S., Matragoon, S., Wei, S., Blaner, W. S., Wang, Y., Liu, C., Gottesman, M. E., & Ripps, H. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-12-04511.1998 · Cited by 116 · cited 2×
“…of sensitivity by the rods as might have been expected if IRBP were critical for the transport of 11-cis retinal to photoreceptors (Palczewski et al., 1999; Ripps et al., 2000); however, Irbp / mice do exhibit rod degeneration (Liou et al., 1998), indicating that IRBP’s absence is not benign.”
Retinoids for treatment of retinal diseases
Palczewski, K. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.03.001 · Cited by 111 · cited 2×
“There has been recent interest in the use of retinoids and small molecules mimicking retinoids as therapeutic agents acting as inhibitors of the visual cycle as a means of preventing the accumulation of the lipofuscin that occurs in Stargardt’s disease and macular degeneration (Golczak et al., 2008; Maiti et al., 2006…”
Breaking the Covalent Bond— A Pigment Property that Contributes to Desensitization in Cones
Kefalov, V. J., Stabio, M. E., Kono, M., Goletz, P. W., Crouch, R. K., Cornwall, M. C., & Yau, K. (2005) · Neuron · doi:10.1016/j.neuron.2005.05.009 · Cited by 110 · cited 1×
“The loss of chromophore was also shown to take place in cones as well as in expressed and purified cone pigments; however, this did not occur with rods and rhodopsin (Kefalov et al., 2005).”
Self-citationExistence of a β-ionone ring-binding site in the rhodopsin molecule
Matsumoto, H., & Yoshizawa, T. (1975) · Nature · doi:10.1038/258523a0 · Cited by 109 · cited 1×
“Compounds representing a fraction of the structure of retinal have been known for some years to fit into the binding site of rhodopsin and to inhibit the binding of the native chromophore (Matsumoto and Yoshizawa, 1975; Nelson et al., 1970).”
Jin, M., Li, S., Nusinowitz, S., Lloyd, M., Hu, J., Radu, R. A., Bok, D., & Travis, G. H. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3882-08.2009 · Cited by 109 · cited 1×
“The isoform of RPE65 appears to affect the phenotype of Irbp / mice as Jin et al. (2009) reported cones in Irbp / mice with the Leu450 variant of RPE65 also had reduced outer segment length, partially mislocalized cone opsin, and underwent progressive degeneration.”
A Visual Pigment Expressed in Both Rod and Cone Photoreceptors
Ma, J.-X., Znoiko, S. L., Othersen, K. L., Ryan, J. C., Das, J., Isayama, T., Kono, M., Oprian, D. D., Corson, D. W., Cornwall, M. C., et al. (2001) · Neuron · doi:10.1016/s0896-6273(01)00482-2 · Cited by 107 · cited 1×
“The salamander green rod has been shown to have the same SWS2 opsin as the blue cone of that species (Ma et al., 2001).”
Self-citationIdentification of DES1 as a vitamin A isomerase in Müller glial cells of the retina
Kaylor, J. J., Yuan, Q., Cook, J., Sarfare, S., Makshanoff, J., Miu, A., Kim, A., Kim, P., Habib, S., Roybal, C. N., et al. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1114 · Cited by 107
Small Molecule RPE65 Antagonists Limit the Visual Cycle and Prevent Lipofuscin Formation
Maiti, P., Kong, J., Kim, S. R., Sparrow, J. R., Allikmets, R. L., & Rando, R. R. (2005) · Biochemistry · doi:10.1021/bi0518545 · Cited by 106 · cited 2×
“There has been recent interest in the use of retinoids and small molecules mimicking retinoids as therapeutic agents acting as inhibitors of the visual cycle as a means of preventing the accumulation of the lipofuscin that occurs in Stargardt’s disease and macular degeneration (Golczak et al., 2008; Maiti et al., 2006…”
Crouch, R. K., Hazard, E. S., Lind, T., Wiggert, B., Chader, G., & Corson, D. W. (1992) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1992.tb02154.x · Cited by 105 · cited 3×
“As IRBP protects the isomeric state of 11-cis retinol, even in the presence of light (Crouch et al., 1992), the protein is likely to have a critical role in the delivery of 11-cis retinol to cones and to facilitate cone function.”
InfluentialSelf-citationZhang, H., Fan, J., Li, S., Karan, S., Rohrer, B., Palczewski, K., Frederick, J. M., Crouch, R. K., & Baehr, W. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.0317-08.2008 · Cited by 101 · cited 2×
“Data to support this come from Lrat / mouse studies (Fan et al., 2008; Zhang et al., 2008), where the lack of esterification of alltrans retinol in the RPE, the substrate for RPE65-dependent isomerization (Moiseyev et al.”
Self-citationJin, J., Crouch, R. K., Corson, D. W., Katz, B. M., MacNichol, E. F., & Cornwall, M. C. (1993) · Neuron · doi:10.1016/0896-6273(93)90155-k · Cited by 98 · cited 1×
“The first observations weremade using salamander rods and cones with measurements on isolated photoreceptors (Isayama et al., 2006; Jin et al., 1993; Kefalov et al., 1999).”
Self-citationRecovery of cone receptor activity in the frog's isolated retina
Hood, D. C., & Hock, P. A. (1973) · Vision Research · doi:10.1016/0042-6989(73)90065-5 · Cited by 95 · cited 1×
“Previous work in the isolated frog retina has also implicated the regeneration of 11-cis retinal by the retina independent of the RPE (Goldstein,1968; Hood and Hock, 1973).”
Rpe65−/−and Lrat−/−Mice: Comparable Models of Leber Congenital Amaurosis
Fan, J., Rohrer, B., Frederick, J. M., Baehr, W., & Crouch, R. K. (2008) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.08-1727 · Cited by 95 · cited 3×
“Data to support this come from Lrat / mouse studies (Fan et al., 2008; Zhang et al., 2008), where the lack of esterification of alltrans retinol in the RPE, the substrate for RPE65-dependent isomerization (Moiseyev et al.”
Self-citationVisual cycle: dependence of retinol production and removal on photoproduct decay and cell morphology
Ala-Laurila, P., Kolesnikov, A. V., Crouch, R. K., Tsina, E., Shukolyukov, S. A., Govardovskii, V. I., Koutalos, Y., Wiggert, B., Estevez, M. E., & Cornwall, M. C. (2006) · The Journal of General Physiology · doi:10.1085/jgp.200609557 · Cited by 95 · cited 3×
“Imaging the fluorescence of retinol has permitted the study of its formation kinetics in isolated photoreceptors from several vertebrate species, including salamander (Ala-Laurila et al., 2006; Tsina et al., 2004), frog (Chen et al.”
Self-citationRipps, H., Peachey, N. S., Xu, X., Nozell, S. E., Smith, S. B., & Liou, G. I. (2000) · Visual Neuroscience · doi:10.1017/s095252380017110x · Cited by 95 · cited 2×
“Knocking out IRBP in mice (Irbp / ) did not affect recovery of sensitivity by the rods as might have been expected if IRBP were critical for the transport of 11-cis retinal to photoreceptors (Palczewski et al., 1999; Ripps et al., 2000); however, Irbp / mice do exhibit rod degeneration (Liou et al.”
McBee, J. K., Kuksa, V., Alvarez, R., de Lera, A. R., Prezhdo, O., Haeseleer, F., Sokal, I., & Palczewski, K. (2000) · Biochemistry · doi:10.1021/bi001061c · Cited by 95 · cited 1×
“The mechanism of action is still unclear, but recent studies support a carbocation mechanism (Redmond et al., 2010) as previously proposed (McBee et al., 2000).”
Golczak, M., Maeda, A., Bereta, G., Maeda, T., Kiser, P. D., Hunzelmann, S., von Lintig, J., Blaner, W. S., & Palczewski, K. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708982200 · Cited by 93 · cited 2×
“There has been recent interest in the use of retinoids and small molecules mimicking retinoids as therapeutic agents acting as inhibitors of the visual cycle as a means of preventing the accumulation of the lipofuscin that occurs in Stargardt’s disease and macular degeneration (Golczak et al., 2008; Maiti et al., 2006…”
Interphotoreceptor retinoid-binding protein––an old gene for new eyes
Gonzalez-Fernandez, F. (2003) · Vision Research · doi:10.1016/j.visres.2003.09.019 · Cited by 92 · cited 2×
“IRBP is the most abundant soluble protein in the sub-retinal space (Gonzalez-Fernandez, 2003) and is known to bind retinoids (Edwards andAdler,1994; Pepperberg et al.,1993).”
Multiple visual pigments in a photoreceptor of the salamander retina.
Makino, C. L., & Dodd, R. L. (1996) · The Journal of General Physiology · doi:10.1085/jgp.108.1.27 · Cited by 91 · cited 1×
“This was first shown for the guppy (Archer and Lythgoe, 1990) and the salamander (Makino and Dodd, 1996).”
Kociok, N., HEPPEKAUSEN, H., Schraermeyer, U., et al. (1998) · Experimental Eye Research · doi:10.1006/exer.1998.0517 · Cited by 89 · cited 2×
“However, themRNA of RPE65 has been reported in the iris (Kociok et al., 1998), and the protein has been found in transformed kidney cells (Ma et al.”
Light-evoked changes in the interphotoreceptor matrix
Uehara, F., Matthes, M. T., Yasumura, D., & LaVail, M. M. (1990) · Science · doi:10.1126/science.2194288 · Cited by 89 · cited 4×
“, 1985), is co-localized with Müller cell processes surrounding the cone cell body (Uehara et al., 1990), and is found in high concentrations around the cones (Carter-Dawson and Burroughs, 1992a, 1992b).”
InfluentialLipofuscin autofluorescence: evidence for vitamin A involvement in the retina
Katz, M. L., Eldred, G. E., & Robison, W. G. (1987) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(87)90088-1 · Cited by 88 · cited 1×
“Third, lipofuscin accumulation requires the phagocytosis of the photoreceptor OS by the RPE, and in the absence of phagocytosis, retinoid-derived fluorescent material accumulates in the photoreceptors (Katz et al., 1987).”
Retinal carotenoids can attenuate formation of A2E in the retinal pigment epithelium
Bhosale, P., Serban, B., & Bernstein, P. S. (2009) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.09.012 · Cited by 85 · cited 3×
“The images are oriented: dorsal e top; ventral e bottom; nasal laboratory utilized 8 mm tissue punches on human RPE and surprisingly found no correlation with the lipofuscin distribution reported by others (Bhosale et al., 2009; Wing et al., 1978).”
Chen, C., Thompson, D. A., & Koutalos, Y. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.354514 · Cited by 85 · cited 2×
“Recent in vitro studies of retinal release from cone opsins after bleaching compared to rhodopsin have shown that cone pigments release retinal at a much faster rate (M.H. Chen et al., 2012; Das et al., 2004; Hunt et al., 2009).”
Self-citationCarmeli, I., Skákalová, V., Naaman, R., & Vager, Z. (2002) · Angewandte Chemie International Edition · doi:10.1002/1521-3773(20020301)41:5 · Cited by 85
Maeda, T., Cideciyan, A. V., Maeda, A., Golczak, M., Aleman, T. S., Jacobson, S. G., & Palczewski, K. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp163 · Cited by 83 · cited 2×
“On the other hand, a detoxifying role for A2E itself has also been suggested as it removes the highly toxic free all-trans retinal (Maeda et al., 2011, 2009a; Roberts et al., 2002).”
METABOLISM OF GLUCOSE AND REDUCTION OF RETINALDEHYDE IN RETINAL PHOTORECEPTORS1
Futterman, S., Hendrickson, A. E., Bishop, P., Rollins, M. H., & Vacano, E. (1970) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1970.tb02195.x · Cited by 82 · cited 1×
“The reduction requires NADPH (Futterman et al., 1970) and, at the same time, achieves both the removal of retinal and the initiation of the recycling of all-trans retinal back to the 11-cis form.”
A retinyl ester hydrolase activity intrinsic to the brush border membrane of rat small intestine
Rigtrup, K. M., & Ong, D. E. (1992) · Biochemistry · doi:10.1021/bi00126a011 · Cited by 80 · cited 1×
“Retinylesters are composed of all-trans retinol bound to a fatty acid through an ester linkage that must be hydrolyzed for absorption to occur (Rigtrup and Ong,1992).”
Photopigment coexpression in mammals: comparative and developmental aspects.
Lukáts, Á., Szabó, A., Röhlich, P., Béla, V. I. G. H., & Szél, Á. (2005) · PubMed · doi:10.14670/hh-20.551 · Cited by 79 · cited 2×
“…studies have shown that several species of rodents, notably thewell characterized and genetically-modified mouse, contain a mixture of the two cone opsins with a well-defined dorsal-ventral gradient across the retina, even in the wild-type animals (Applebury et al., 2000; Lukáts et al., 2005).”
Roberts, J. E., Kukielczak, B. M., Hu, D., Miller, D. S., Bilski, P. J., Sik, R. H., Motten, A. G., & Chignell, C. F. (2002) · Photochemistry and Photobiology · doi:10.1562/0031-8655(2002)0750184troaip2.0.co2 · Cited by 79
Wald, G. (1951) · Science · doi:10.1126/science.113.2933.287 · Cited by 75 · cited 1×
“1 for retinoid structures) as its chromophore (Wald, 1935, 1951).”
Loss of cone molecular markers in rhodopsin-mutant human retinas with retinitis pigmentosa.
John, S. K., Smith, J. E., Aguirre, G. D., & Milam, A. H. (2000) · PubMed · Cited by 74
Oxidation of A2E Results in the Formation of Highly Reactive Aldehydes and Ketones
Wang, Z., Keller, L. M. M., Dillon, J. P., & Gaillard, E. R. (2006) · Photochemistry and Photobiology · doi:10.1562/2006-04-01-ra-864 · Cited by 74 · cited 1×
“There are numerous studies suggesting a toxic role for A2E to the RPE, particularly in its oxidized form (Kim et al., 2008; Wang et al., 2006).”
Von selbstorganisierenden Polymeren zu Nanohybrid- und Biomaterialien
Förster, S., & Plantenberg, T. (2002) · Angewandte Chemie · doi:10.1002/1521-3757(20020301)114:5 · Cited by 73
The implications of rod-dependent cone survival for basic and clinical research.
Hicks, D., & Sahel, J. (1999) · PubMed · Cited by 71
Accessibility of the iodopsin chromophore
Matsumoto, H., Tokunaga, F., & Yoshizawa, T. (1975) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(75)90337-2 · Cited by 70 · cited 2×
“Retinal is a reactive aldehyde and a photosensitizer (Delmelle, 1978; Krasnovsky and Kagan, 1979; Matsumoto et al., 1975; Rozanowska and Sarna, 2005), and its toxicity may play a role in several diseases of the retina.”
Fleisch, V. C., Schonthaler, H. B., von Lintig, J., & Neuhauss, S. C. F. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2367-08.2008 · Cited by 68 · cited 1×
“Knocking down the expression of CRALBP in the Müller cells of zebrafish larvae by using antisense morpholinos results in a substantial decrease in 11-cis retinal and reduction in light sensitivity, supporting the key role of this protein (Collery et al., 2008; Fleisch et al., 2008).”
Nutritional and inherited blindness in the rat
Dowling, J. E. (1964) · Experimental Eye Research · doi:10.1016/s0014-4835(64)80042-7 · Cited by 68 · cited 1×
“Night blindness resulting from vitamin A deficiency was identified as the result of the rod photoreceptors lacking chromophore (Dowling, 1964), and indeed many of these studies led to the initial findings in retinoid cycling.”
RETINAL SENSITIZED PHOTODYNAMIC DAMAGE TO LIPOSOMES
Delmelle, M. (1978) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1978.tb07718.x · Cited by 67 · cited 1×
“Retinal is a reactive aldehyde and a photosensitizer (Delmelle, 1978; Krasnovsky and Kagan, 1979; Matsumoto et al., 1975; Rozanowska and Sarna, 2005), and its toxicity may play a role in several diseases of the retina.”
[46] Genetic analysis of RPE65: From human disease to mouse model
Redmond, T. M., & Hamel, C. (2000) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(00)16758-8 · Cited by 66 · cited 1×
“Using a polyclonal anti-RPE65 antibody generated from a synthetic peptide corresponding to residues 150e164 of bovine RPE65 (NFITKVNPETLETIK) (Redmond and Hamel, 2000), we showed localization of RPE65 in the OS of cones of thewild-type mice (Fig.”
Inhibitors of retinyl ester formation also prevent the biosynthesis of 11-cis-retinol
Trehan, A., Cañada, F. J., & Rando, R. R. (1990) · Biochemistry · doi:10.1021/bi00454a001 · Cited by 66 · cited 1×
“Themost common ester found in the retina is retinyl-palmitate (Trehan et al., 1990).”
RPE65 is essential for the function of cone photoreceptors in NRL-deficient mice
Wenzel, A., von Lintig, J., Oberhauser, V., Tanimoto, N., Grimm, C., & Seeliger, M. W. (2007) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.06-0652 · Cited by 66 · cited 3×
“Further support for the existence of RPE65 in mouse cones comes from the Nrl / mouse, which contains elevated levels of RPE65 within the retinawhen compared to the wild-type mouse (Wenzel et al., 2007).”
RPE65, Visual Cycle Retinol Isomerase, Is Not Inherently 11-cis-specific
Redmond, T. M., Poliakov, E., Kuo, S., Chander, P., & Gentleman, S. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.027458 · Cited by 65 · cited 4×
“Surprisingly, the RPE65-based complex is not specific for the 11-cis isomer, but may be driven by a mass action effect of the binding protein(s) (Redmond et al., 2010).”
InfluentialChen, C., Tsina, E. K., Cornwall, M. C., Crouch, R. K., Vijayaraghavan, S., & Koutalos, Y. (2004) · Biophysical Journal · doi:10.1529/biophysj.104.054254 · Cited by 64 · cited 2×
“, 2004), frog (Chen et al., 2005; Wu et al., 2007), gecko (Kolesnikov et al.”
Self-citationWu, Q., Blakeley, L. R., Cornwall, M. C., Crouch, R. K., Wiggert, B. O., & Koutalos, Y. (2007) · Biochemistry · doi:10.1021/bi7004619 · Cited by 64 · cited 2×
“, 2004), frog (Chen et al., 2005; Wu et al., 2007), gecko (Kolesnikov et al.”
Self-citationA novel cone visual cycle in the cone-dominated retina
Muniz, A., Villazana-Espinoza, E. T., Hatch, A. L., Trevino, S. G., Allen, D. M., & Tsin, A. T. C. (2007) · Experimental Eye Research · doi:10.1016/j.exer.2007.05.003 · Cited by 60 · cited 1×
“5; for reviews, see Muniz et al., 2007; Wang and Kefalov, 2011; Wolf, 2004).”
Palmitoylation stabilizes unliganded rod opsin
Maeda, A., Okano, K., Park, P. S. ‐., Lem, J., Crouch, R. K., Maeda, T., & Palczewski, K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000640107 · Cited by 59 · cited 1×
“Several studies have shown that removal of the palmitate groups on rhodopsin has little effect on the functional properties except, surprisingly, that excessive light greatly accelerates retinal degeneration compared to wild-type animals (Maeda et al., 2010; Wang et al., 2005).”
Self-citation11-cis- and All-trans-Retinols Can Activate Rod Opsin: Rational Design of the Visual Cycle
Kono, M., Goletz, P. W., & Crouch, R. K. (2008) · Biochemistry · doi:10.1021/bi800357b · Cited by 56 · cited 1×
“Interestingly, 11-cis retinol is now known to act as an agonist to rod opsin, activating the rod opsins in a light-independent manner (Kono et al., 2008).”
Self-citationRdh12 activity and effects on retinoid processing in the murine retina
Chrispell, J. D., Feathers, K. L., Kane, M. A., Kim, C. Y., Brooks, M., Khanna, R., Kurth, I., Hübner, C. A., Gal, A., Mears, A. J., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.020966 · Cited by 56 · cited 1×
“Consistent with this notion, mice that lack retinol dehydrogenases, the enzymes that oxidize all-trans retinol to retinal show increased A2E accumulation in the RPE (Chrispell et al., 2009; Maeda et al., 2005).”
Collery, R., McLoughlin, S., Vendrell, V., Finnegan, J., Crabb, J. W., Saari, J. C., & Kennedy, B. N. (2008) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.08-1957 · Cited by 56 · cited 1×
“Knocking down the expression of CRALBP in the Müller cells of zebrafish larvae by using antisense morpholinos results in a substantial decrease in 11-cis retinal and reduction in light sensitivity, supporting the key role of this protein (Collery et al., 2008; Fleisch et al., 2008).”
Highly efficient retinal metabolism in cones
Miyazono, S., Shimauchi-Matsukawa, Y., Tachibanaki, S., & Kawamura, S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806593105 · Cited by 55 · cited 1×
“This is in agreement with the faster release of retinal from the photoactivated visual pigment, and the higher retinol dehydrogenase activity in cones (Miyazono et al., 2008).”
Fukada, Y., Okano, T., Shichida, Y., Yoshizawa, T., Trehan, A., Mead, D., Denny, M., Asato, A. E., & Liu, R. S. H. (1990) · Biochemistry · doi:10.1021/bi00464a033 · Cited by 54 · cited 1×
“Hydroxylamine, which can disrupt the Schiff base linkage of 11-cis retinal by forming an oxime, has greater accessibility to the chromophore in the dark in most cone pigments than in rhodopsin (Fukada et al., 1990; Wald et al., 1955).”
Localization of retinoid-binding proteins in developing rat retina
Eisenfeld, A. J., Bunt-Milam, A. H., & Saari, J. C. (1985) · Experimental Eye Research · doi:10.1016/s0014-4835(85)80020-8 · Cited by 54 · cited 1×
“Müller cells contain CRBP and CRALBP, both of which are retinoid binding proteins found in the RPE, with the latter preferentially binding 11-cis retinoids (Bunt-Milam and Saari, 1983; Eisenfeld et al., 1985).”
Spatial localization of A2E in the retinal pigment epithelium
Grey, A. C., Crouch, R. K., Koutalos, Y., Schey, K. L., & Ablonczy, Z. (2011) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.10-7020 · Cited by 52 · cited 1×
“We have recently developed a method for the localization of bis-retinoid utilizing a mass spectrometry-based technique, MALDI imaging (Grey et al., 2011).”
MethodSelf-citationMakaretz, M., & Levine, R. L. (1980) · Vision Research · doi:10.1016/0042-6989(80)90092-9 · Cited by 52 · cited 1×
“(AeB) Cross-section of lizard retina stained with Hematoxylin/Eosin (H&E) or Periodic Acid Schiff (PAS) shows cones with large IS and tapered OS, as previously described (Makaretz and Levine, 1980).”
Krasnovsky, А. А., & Kagan, V. E. (1979) · FEBS Letters · doi:10.1016/0014-5793(79)81198-9 · Cited by 50 · cited 1×
“Retinal is a reactive aldehyde and a photosensitizer (Delmelle, 1978; Krasnovsky and Kagan, 1979; Matsumoto et al., 1975; Rozanowska and Sarna, 2005), and its toxicity may play a role in several diseases of the retina.”
Parker, R., Wang, J.-S., Kefalov, V. J., & Crouch, R. K. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3722-10.2011 · Cited by 49 · cited 3×
“Further demonstration of oxidase activity in cones was shown in eyecups of mice that lacked endogenous 11-cis retinal from which 11-cis retinal could be generated after incubation with 11-cis retinol (Parker et al., 2011).”
InfluentialSelf-citationMechanisms involved in A2E oxidation
Kim, S. R., Steffen Jockusch, B., Itagaki, Y., Turro, N. J., & Sparrow, J. R. (2008) · Experimental Eye Research · doi:10.1016/j.exer.2008.03.016 · Cited by 49 · cited 1×
“There are numerous studies suggesting a toxic role for A2E to the RPE, particularly in its oxidized form (Kim et al., 2008; Wang et al., 2006).”
Normal cone function requires the interphotoreceptor retinoid binding protein
Parker, R. O., Fan, J., Nickerson, J. M., Liou, G. I., & Crouch, R. K. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.0063-09.2009 · Cited by 48 · cited 2×
“Cones in Irbp / mice were found to be retinoid-deficient under photopic conditions in two studies (Parker et al., 2009), leading to the proposal that 11-cis retinol supplies are disrupted in the absence of IRBP.”
Self-citationSun, H. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.06.010 · Cited by 47 · cited 1×
“STRA6, the recently identified membrane receptor for plasma retinol binding protein (RPB), mediates the cellular uptake of trans retinol into the RPE (Kawaguchi et al., 2007; Sun, 2012).”
Tsina, E. K., Chen, C., Koutalos, Y., Ala‐Laurila, P., Tsacopoulos, M., Wiggert, B. O., Crouch, R. K., & Cornwall, M. C. (2004) · The Journal of General Physiology · doi:10.1085/jgp.200409078 · Cited by 46 · cited 2×
“Imaging the fluorescence of retinol has permitted the study of its formation kinetics in isolated photoreceptors from several vertebrate species, including salamander (Ala-Laurila et al., 2006; Tsina et al., 2004), frog (Chen et al.”
Self-citationRapid Release of Retinal from a Cone Visual Pigment following Photoactivation
Chen, M.-H., Kuemmel, C., Birge, R. R., & Knox, B. E. (2012) · Biochemistry · doi:10.1021/bi201522h · Cited by 46 · cited 2×
“Recent in vitro studies of retinal release from cone opsins after bleaching compared to rhodopsin have shown that cone pigments release retinal at a much faster rate (M.H. Chen et al., 2012; Das et al., 2004; Hunt et al., 2009).”
Movement of retinal along cone and rod photoreceptors
Jin, J., Jones, G. J., & Cornwall, M. C. (1994) · Visual Neuroscience · doi:10.1017/s0952523800001735 · Cited by 46 · cited 1×
“Using suction electrodes to mask the OS of isolated salamander rods and cones, 11-cis retinal presented to the cell bodies of bleached photoreceptors restored light sensitivity in cones, but had no effect on rods (Jin et al., 1994).”
Tsilou, E. T., Hamel, C., Yu, S., & Redmond, T. M. (1997) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1997.0276 · Cited by 45 · cited 2×
“RPE65 has been well-documented to be abundant in the RPE of many species (Hamel et al., 1993; Tsilou et al., 1997) and was originally proposed to be specific to that tissue.”
Tang, P. H., Buhusi, M. C., Ma, J.-X., & Crouch, R. K. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.4265-11.2011 · Cited by 45 · cited 11×
“In humans, RPE65 appears to be selectively expressed in the OS regions of cones that detect green/red light, but not in blue cones (Tang et al., 2011a).”
InfluentialCloning and localization of RPE65 mRNA in salamander cone photoreceptor cells
Ma, J., Xu, L., Othersen, D. K., Redmond, T. M., & Crouch, R. K. (1998) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(98)00221-8 · Cited by 44 · cited 1×
“RT-PCR analysis of isolated salamander photoreceptors first demonstrated the presence of RPE65 mRNA in cones, but not rods (Ma et al., 1998).”
Self-citationWang, Z., Wen, X., Ablonczy, Z., Crouch, R. K., Makino, C. L., & Lem, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502588200 · Cited by 44 · cited 1×
“Several studies have shown that removal of the palmitate groups on rhodopsin has little effect on the functional properties except, surprisingly, that excessive light greatly accelerates retinal degeneration compared to wild-type animals (Maeda et al., 2010; Wang et al., 2005).”
Self-citationKefalov, V. J., Cornwall, M. C., & Crouch, R. K. (1999) · The Journal of General Physiology · doi:10.1085/jgp.113.3.491 · Cited by 43 · cited 1×
“The first observations weremade using salamander rods and cones with measurements on isolated photoreceptors (Isayama et al., 2006; Jin et al., 1993; Kefalov et al., 1999).”
Self-citationThe action of 11-cis retinol on cone opsins and intact cone photoreceptors
Ala-Laurila, P., Cornwall, M. C., Crouch, R. K., & Kono, M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.004697 · Cited by 40 · cited 4×
“11-cis Retinal serves as an inverse agonist to the opsins (Ala-Laurila et al., 2009) resulting in a reduction of the photoreceptor resting current.”
InfluentialSelf-citationRole of the 9-Methyl Group of Retinal in Cone Visual Pigments
Das, J., Crouch, R. K., Ma, J., et al. (2004) · Biochemistry · doi:10.1021/bi036097u · Cited by 38 · cited 6×
“ND ¼ not determined. a Data from Das et al. (2004). b Unpublished data from Kono and Crouch although a spectrum of 11-cis 13-demethyl retinal in bovine RH1 (Nelson et al., 1970) and an action spectrum of salamander rods regenerated with the same analog have been shown to have the same absorption…”
MethodInfluentialSelf-citation13-Desmethyl Rhodopsin and 13-Desmethyl Isorhodopsin: Visual Pigment Analogues
Nelson, R., DeRiel, J. K., & Kropf, A. (1970) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.66.2.531 · Cited by 38 · cited 6×
“Rhodopsin falls into the RH1 class of opsins; the human blue cone opsin is one form of a short wavelength-sensitive (SWS1) opsin that includes pigments that absorb maximally from about 350 to 440 nm; and the human red and green cone opsins are both medium/long wavelength-sensitive (M/LWS) opsins, which account for the…”
InfluentialIRBP enhances removal of 11-cis retinaldehyde from isolated RPE membranes
EDWARDS, R. B., & ADLER, A. J. (2000) · Experimental Eye Research · doi:10.1006/exer.1999.0781 · Cited by 37 · cited 2×
“In vitrodata from several laboratories have shown that IRBP facilitates clearance of all-trans retinol from photoreceptor cells and uptake of 11-cis retinal from the RPE (Edwards and Adler, 2000; Jones et al., 1989).”
InfluentialVisual pigments and the early receptor potential of the isolated frog retina
Goldstein, E. B. (1968) · Vision Research · doi:10.1016/0042-6989(68)90070-9 · Cited by 36
Evidence for Two Retinoid Cycles in the Cone-Dominated Chicken Eye
Muniz, A., Betts, B. S., Trevino, A. R., Buddavarapu, K., Roman, R., Ma, J., & Tsin, A. T. C. (2009) · Biochemistry · doi:10.1021/bi9002937 · Cited by 35 · cited 2×
“…the LRAT-dependent retinol esterification in the RPE, microsomes of chicken retina generated 11-cis retinyl-ester from all-trans retinol through a mechanism requiring palm-CoA as an acyl donor, suggesting this isomerase is dependent on acyl CoA-retinol acyltransferase (ARAT) (Muniz et al., 2009).”
The visual cycle of the cone photoreceptors of the retina
(2004) · Nutrition Reviews · doi:10.1111/j.1753-4887.2004.tb00053.x · Cited by 34 · cited 2×
“5; for reviews, see Muniz et al., 2007; Wang and Kefalov, 2011; Wolf, 2004).”
Formation of all- trans Retinol after Visual Pigment Bleaching in Mouse Photoreceptors
Chen, C., Blakeley, L. R., & Koutalos, Y. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-3336 · Cited by 34 · cited 2×
“Retinas obtained from (A) C57BL/6 or ght field; middle ¼ fluorescence images before bleaching; and the right panel ¼ after ars ¼ 5 mm. Data re-plotted from Chen et al. (2009). precursors of lipofuscin, such as A2PE, form in the photoreceptor OS from all-trans retinal that is escaping reduction to…”
Self-citationThe spatial relationship between Mu¨ller cell processes and the photoreceptor output synapse
Sarantis, M., & Mobbs, P. G. (1992) · Brain Research · doi:10.1016/0006-8993(92)90909-s · Cited by 34 · cited 1×
“This finding is particularly interesting considering the topology of Müller cell processes, as they make numerous associations with cones at this region (Sarantis and Mobbs, 1992; Wang et al., 2009).”
Sakai, T., Furukawa, T., Iwanari, H., Oka, C., Nakano, T., Kawaichi, M., & Honjo, T. (1995) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a124955 · Cited by 33 · cited 2×
“, 2010), but the best-studied bis-retinoid is still A2E (Eldred and Lasky, 1993; Parish et al., 1998; Sakai et al., 1995).”
Excited state properties and in vitro phototoxicity studies of three phenothiazine derivatives
F., E., L., L., G., A., et al. (2002) · Pure Amsterdam UMC · doi:10.1562/0031-8655(2002)075 · Cited by 33
RPE65 surface epitopes, protein interactions, and expression in rod- and cone-dominant species.
Hemati, N., Feathers, K. L., Chrispell, J. D., Reed, D. M., Carlson, T. J., & Thompson, D. A. (2005) · PubMed · Cited by 32
Effective and Sustained Delivery of Hydrophobic Retinoids to Photoreceptors
Tang, P. H., Fan, J., Goletz, P. W., Wheless, L., & Crouch, R. K. (2010) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.10-5766 · Cited by 29 · cited 2×
“Methods of sustained delivery of the retinoids have also been developed for the potential use of these hydrophobic agents (Tang et al., 2010).”
Self-citationVisual cycle and its metabolic support in gecko photoreceptors
Kolesnikov, A. V., Ala‐Laurila, P., Shukolyukov, S. A., Crouch, R. K., Wiggert, B. O., Stabio, M. E., GOVARDOVSKII, V. I., & Cornwall, M. C. (2006) · Vision Research · doi:10.1016/j.visres.2006.08.024 · Cited by 28 · cited 2×
“, 2007), gecko (Kolesnikov et al., 2007), and mouse (Blakeley et al.”
Self-citationIdentification of RPE65 in transformed kidney cells1
Ma, J.-X., Zhang, D., Laser, M., Brownlee, N. A., Re, G. G., Hazen‐Martin, D. J., Redmond, T. M., & Crouch, R. K. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00606-7 · Cited by 27 · cited 2×
“, 1998), and the protein has been found in transformed kidney cells (Ma et al., 1999), human epidermis (Hinterhuber et al.”
Self-citationRegeneration of Photopigment Is Enhanced in Mouse Cone Photoreceptors Expressing RPE65 Protein
Tang, P. H., Wheless, L., & Crouch, R. K. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0182-11.2011 · Cited by 26 · cited 11×
“In humans, RPE65 appears to be selectively expressed in the OS regions of cones that detect green/red light, but not in blue cones (Tang et al., 2011a).”
InfluentialSelf-citationRetinoid processing in cone and Müller cell lines
Kanan, Y., Kasus‐Jacobi, A., Moiseyev, G. P., Sawyer, K., Ma, J., & Al‐Ubaidi, M. R. (2007) · Experimental Eye Research · doi:10.1016/j.exer.2007.11.006 · Cited by 25 · cited 2×
“, 2004) are known to have retinol esterase activity (Kanan et al., 2008), and we found that 11-cis retinol can be esterified in these cells (Tang et al.”
Hinterhuber, G., Cauza, K., Brugger, K., Dingelmaier-hovorka, R., Wolff, K., Foedinger, D., & Horvat, R. (2004) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2004.22216.x · Cited by 25 · cited 2×
“, 1999), human epidermis (Hinterhuber et al., 2004), and non-melanocytic skin tumors (Hinterhuber et al.”
Leber's Congenital Amaurosis and RPE65
Harris, E. W. (2001) · International Ophthalmology Clinics · doi:10.1097/00004397-200101000-00008 · Cited by 24 · cited 1×
“Mutations to RPE65 are associated with Type 2 Leber congenital amaurosis (LCA2), an early onset congenital blindness that reduces or abolishes the innate synthesis of 11-cis retinal (Harris, 2001; Marlhens et al., 1997).”
Blakeley, L. R., Chen, C.-K., Chen, C.-K., Chen, J., Crouch, R. K., Travis, G. H., & Koutalos, Y. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-6694 · Cited by 23 · cited 1×
“…the study of its formation kinetics in isolated photoreceptors from several vertebrate species, including salamander (Ala-Laurila et al., 2006; Tsina et al., 2004), frog (Chen et al., 2005; Wu et al., 2007), gecko (Kolesnikov et al., 2007), and mouse (Blakeley et al., 2011; Chen et al., 2009).”
Self-citationCorson, D. W., Kefalov, V. J., Cornwall, M. C., & Crouch, R. K. (2000) · The Journal of General Physiology · doi:10.1085/jgp.116.2.283 · Cited by 23 · cited 1×
“…from Das et al. (2004). b Unpublished data from Kono and Crouch although a spectrum of 11-cis 13-demethyl retinal in bovine RH1 (Nelson et al., 1970) and an action spectrum of salamander rods regenerated with the same analog have been shown to have the same absorption maximum (Corson et al., 2000).”
Self-citationStabio, M. E., Kolesnikov, A. V., Ala‐Laurila, P., Crouch, R. K., GOVARDOVSKII, V. I., & Cornwall, M. C. (2009) · The Journal of General Physiology · doi:10.1085/jgp.200910232 · Cited by 20 · cited 1×
“Consistent with these results, studies have demonstrated that a prolonged light-activated salamander red cone occurs in isolated salamander red cone cells regenerated with 11-cis 9-demethyl retinal (Estevez et al., 2006, 2009).”
Self-citationTakahashi, Y., Moiseyev, G. P., Chen, Y., & Ma, J. (2006) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.06-0614 · Cited by 19 · cited 2×
“This 61 kDa protein undergoes post-translational modification with palmitates to facilitate association with membranes (Takahashi et al., 2006) and is homologous to beta-carotene oxygenases (Redmond et al.”
The gecko visual pigment: the dark exchange of chromophore
Crescitelli, F. (1984) · Vision Research · doi:10.1016/s0042-6989(84)80004-8 · Cited by 18 · cited 1×
“Furthermore, chromophore has been demonstrated to be exchanged in the dark with cone pigments, but not rhodopsin (Crescitelli, 1984; Matsumoto et al., 1975).”
Differences in the pharmacological activation of visual opsins
Isayama, T., Chen, Y., Kono, M., DeGrip, W. J., Ma, J., Crouch, R. K., & Makino, C. L. (2006) · Visual Neuroscience · doi:10.1017/s0952523806230256 · Cited by 18 · cited 2×
“The first observations weremade using salamander rods and cones with measurements on isolated photoreceptors (Isayama et al., 2006; Jin et al., 1993; Kefalov et al., 1999).”
Self-citationExchange of retinol between IRBP and CRBP
Edwards, R. B., & Adler, A. J. (1994) · Experimental Eye Research · doi:10.1006/exer.1994.1094 · Cited by 18 · cited 1×
“The shuttling of all-trans retinol from the photoreceptors to the RPE and 11-cis retinal from the RPE to the photoreceptors is presumably aided by a retinoid binding protein, interphotoreceptor retinoid binding protein (IRBP) (see Section 3.3) (Edwards and Adler, 1994, 2000).”
InfluentialMolecule-Specific Imaging and Quantitation of A2E in the RPE
Ablonczy, Z., Gutierrez, D. B., Grey, A. C., Schey, K. L., & Crouch, R. K. (2011) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-0631-0_11 · Cited by 17 · cited 2×
“Our recent findings that RPE65, the proposed isomerase in the RPE, is present within cones (Tang et al., 2011a, 2011b), and the unexpected distribution of the retinoid metabolite N-retinylidene-N-retinylethanolamine (A2E) (Ablonczy et al., 2012a, and see Fig.”
Self-citationAblonczy, Z., Kono, M., Knapp, D. R., et al. (2006) · Vision Research · doi:10.1016/j.visres.2006.08.003 · Cited by 15 · cited 2×
“SWS2 cone opsins have a single corresponding cysteine, and partial palmitoylation of salamander SWS2 cone opsin has been shown (Ablonczy et al., 2006).”
Self-citationLipofuscin and A2E Accumulate with Age in the Retinal Pigment Epithelium of Nrl−/− Mice†
Boyer, N. P., Tang, P. H., Higbee, D., Ablonczy, Z., Crouch, R. K., & Koutalos, Y. (2012) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2012.01127.x · Cited by 14 · cited 1×
“A2E formation from 11-cis retinal While it is clear that retinoids are involved in lipofuscin, recent evidence shows 11-cis retinal itself may be a major source of lipofuscin andA2E (Boyer et al., 2012).”
Self-citationAmemiya, T. (1975) · Histochemistry and Cell Biology · doi:10.1007/bf00492446 · Cited by 14 · cited 1×
“This structure is known to be composed of smooth ER and glycogen (Amemiya, 1975; Braekevelt, 1990); of a human retina immunostained for RPE65 shows the protein is localized within the uorescence, (B) composite of RPE65 and propidium iodide fluorescence, and (C) RPE65 . however the implications for…”
Retinal photoreceptor fine structure in the mallard duck (Anas platyrhynchos).
Braekevelt, C. R. (1990) · PubMed · Cited by 13
Carter‐Dawson, L. D., & Burroughs, M. (1992) · PubMed · Cited by 13
Hinterhuber, G., Cauza, K., Dingelmaier‐Hovorka, R., et al. (2005) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2005.06769.x · Cited by 13 · cited 2×
“, 2004), and non-melanocytic skin tumors (Hinterhuber et al., 2005).”
Turning Cones Off: the Role of the 9-Methyl Group of Retinal in Red Cones
Stabio, M. E., Ala‐Laurila, P., Crouch, R. K., & Cornwall, M. C. (2006) · The Journal of General Physiology · doi:10.1085/jgp.200609630 · Cited by 11 · cited 1×
“Consistent with these results, studies have demonstrated that a prolonged light-activated salamander red cone occurs in isolated salamander red cone cells regenerated with 11-cis 9-demethyl retinal (Estevez et al., 2006, 2009).”
Self-citationCarter‐Dawson, L. D., & Burroughs, M. (1992) · PubMed · Cited by 10
In Vitro Assays of Rod and Cone Opsin Activity: Retinoid Analogs as Agonists and Inverse Agonists
Kono, M., & Crouch, R. K. (2010) · Methods in molecular biology · doi:10.1007/978-1-60327-325-1_4 · Cited by 8 · cited 1×
“Unexpectedly, it was found that such small molecules could also act as agonists or inverse agonists to opsins (Kono and Crouch, 2010, 2011).”
Self-citationProbing Human Red Cone Opsin Activity with Retinal Analogues
Kono, M., & Crouch, R. K. (2011) · Journal of Natural Products · doi:10.1021/np100749j · Cited by 8 · cited 2×
“a ligand-dependent manner as previously described (Kono and Crouch, 2011).”
Self-citationFan, J., Crouch, R. K., & Kono, M. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-6437 · Cited by 7 · cited 1×
“The small molecules have the advantage in not being light sensitive and also in not forming photoreactive pigments with the opsins (Fan et al., 2011).”
Self-citationLinking Retinoids To Clinical Patterns Of Amd
Ablonczy, Z., Higbee, D., Hanneken, A. M., et al. (2012) · Investigative Ophthalmology & Visual Science · Cited by 1
Self-citation
Cited by
Sorted by citations
Non-syndromic retinitis pigmentosa
Verbakel, S. K., van Huet, R. A. C., Boon, C. J. F., den Hollander, A. I., Collin, R. W. J., Klaver, C. C. W., Hoyng, C. B., Roepman, R., & Klevering, B. J. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.03.005 · Cited by 973
“8); this cycle regenerates 11-cis-retinal at a 20-fold faster rate (Mata et al., 2002; Tang et al., 2013), although all of the proteins in this cycle have not yet been identified.”
Chemistry of the Retinoid (Visual) Cycle
Kiser, P. D., Golczak, M., & Palczewski, K. (2014) · Chemical Reviews · doi:10.1021/cr400107q · Cited by 353
Noncanonical autophagy promotes the visual cycle
Kim, J.-Y., Zhao, H., Martinez, J., Doggett, T. A., Kolesnikov, A. V., Tang, P. H., Ablonczy, Z., Chan, C.-C., Zhou, Z., Green, D. R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.012 · Cited by 347
“The visual cycle is a series of biochemical reactions within the RPE and retina that is fundamental to vision (Tang et al., 2013; Travis et al., 2007).”
InfluentialSelf-citationAutophagy in the eye: Development, degeneration, and aging
Boya, P., Esteban‐Martínez, L., Serrano‐Puebla, A., Gómez‐Sintes, R., & Villarejo‐Zori, B. (2016) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2016.08.001 · Cited by 236
Deletion of autophagy inducer RB1CC1 results in degeneration of the retinal pigment epithelium
Yao, J., Jia, L., Khan, N., Lin, C., Mitter, S. K., Boulton, M. E., Dunaief, J. L., Klionsky, D. J., Guan, J.-L., Thompson, D. A., et al. (2015) · Autophagy · doi:10.1080/15548627.2015.1041699 · Cited by 130
“In addition, vitamin A re-enters the visual cycle for re-isomerization and transport back to the photoreceptors for regeneration of the opsin visual pigments.(54) Our data confirm that in our model we successfully deleted Rb1cc1 from the RPE, and in this manner we were able to selectively prevent induction of canonica…”
Background
Metadata
- Authors
- Tang, P. H., Kono, M., Koutalos, Y., Ablonczy, Z., & Crouch, R. K.
- Affiliations
- Medical University of South Carolina (US)
- Corresponding author
- Crouch, Rosalie K.
- Venue
- Progress in Retinal and Eye Research
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 32
- Pages
- 48-63
- ISSN
- 1350-9462 (ISSN-L)
- PMC
- PMC3746031
- OpenAlex
- W2046951190
- Cited by
- 122
- References
- 194
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 4 · 2023: 7 · 2022: 3 · 2021: 6 · 2020: 16 · 2019: 4 · 2018: 10 · 2017: 12 · 2016: 7 · 2015: 17 · 2014: 12 · 2013: 11
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Progress in Retinal and Eye Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1c06rr015455-01a1)
- National Eye Institute (R01EY019065, R01EY014850, R21EY020661, R01EY019515, R01EY004939)
- National Center for Research Resources (C06 RR-015455, P41RR008605)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Keywords
- retinoid cycle, 11-cis-retinal, vitamin A metabolism, chromophore regeneration, photoreceptors, rods, cones, RPE65, retinoid transport, visual pigments, G protein-coupled receptors, posterior segment of the eye
- MeSH terms
- Animals, Eye Proteins, Humans, Retina, Retinal Pigments, Retinoids, Retinal Cone Photoreceptor Cells
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