The cell biology of the retinal pigment epithelium

In the paper

“In addition to Na+/K+-ATPase, polarized expression of other ion pumps and channels help regulate the environment around the photoreceptors, which is important for photoreceptor electrophysiology and viability (Wimmers et al., 2007).”

What the sources say

• Not checked yetcites Wimmers et al., 2007 source

In the paper

“However, electroporation or nucleofection has been reported to yield transfection efficiencies of ~20–40% (Toops et al., 2014).”

What the sources say

• Not checked yetcites Toops et al., 2014 source

In the paper

“In the human eye, each RPE cell takes care of ~30 photoreceptors (Osterberg, 1935), which places a unique burden on the degradative machinery of the cell.”

What the sources say

• Not checked yetcites Osterberg, 1935

In the paper

“Second, non-viral lipid-based gene transfection is less efficient in primary RPE due to their post-mitotic nature.”

In the paper

“There are now published protocols using directed approaches that provide relatively efficient differentiation into cultures of cells, reported to possess a wide range of RPE characteristics, including gene expression, polarized organization, and physiological and cell biological functions (Idelson et al., 2009; Buchholz et al., 2013; Gong et al., 2015; Maruotti et al., 2015; Hazim et al., 2017).”

What the sources say

• Not checked yetcites Idelson et al., 2009 source
• Not checked yetcites Buchholz et al., 2013 source
• Not checked yetcites Gong et al., 2015 source

In the paper

“The RPE also takes care of the catabolic phase of the turnover of OS disk membranes, by phagocytosing the distal OS disks and degrading them (Young and Bok, 1969).”

What the sources say

• Not checked yetcites Young and Bok, 1969

In the paper

“Detailed protocols to develop cultures from adult human donors have been established and are reported to yield highly polarized RPE monolayers after at least 4 weeks in culture (Blenkinsop et al., 2013).”

What the sources say

• Not checked yetcites Blenkinsop et al., 2013 source

In the paper

“The TER is a critical measure of the barrier function of the RPE, which is established by the expression and circumferential localization of tight junction proteins, such as zonula occludens (ZO)-1, occludin, and specific claudins (Rahner et al., 2004; Peng et al., 2011).”

What the sources say

• Not checked yetcites Rahner et al., 2004 source
• Not checked yetcites Peng et al., 2011 source

In the paper

“Nevertheless, given the limited availability of human donor tissues, well-polarized primary RPE cultures from laboratory rodents and farm animals provide valuable models for studying RPE biology and disease pathogenesis.”

In the paper

“These cultures also have a high trans-epithelial electrical resistance (TER), from 500 to over 800 Ω cm2 (Hu and Bok, 2001; Maminishkis et al., 2006; Sonoda et al., 2009).”

What the sources say

• Not checked yetcites Hu and Bok, 2001
• Not checked yetcites Maminishkis et al., 2006 source
• Not checked yetcites Sonoda et al., 2009 source

In the paper

“The isomerization of this all-trans-retinal back to 11-cis-retinal is a central event in the visual cycle that occurs in the RPE (Wald and Brown, 1956).”

What the sources say

• Not checked yetcites Wald and Brown, 1956

In the paper

“A striking example of this is expression of the β2 subunit of the Na+/K+-ATPase, which results in the localization of this pump to the apical surface, rather than the basolateral surface, as found in most other epithelia (Lobato-Alvarez et al., 2016).”

What the sources say

• Not checked yetcites Lobato-Alvarez et al., 2016 source

In the paper

“With the introduction of microscopic autoradiography, Droz (1963) was able to determine that proteins were synthesized in the photoreceptor inner segments, and, with time, migrated from the inner segments to the outer segments.”

What the sources say

• Not checked yetcites Droz, 1963

In the paper

“Over the years, with numerous passages, the ability of cells of this line to demonstrate characteristics of differentiated RPE has diminished (Strunnikova et al., 2010; Lehmann et al., 2014).”

What the sources say

• Not checked yetcites Strunnikova et al., 2010 source
• Not checked yetcites Lehmann et al., 2014 source

In the paper

“Human fetal RPE cultures carrying a complement factor H risk haplotype were found to have an increased susceptibility to oxidative stress and complement attack when fed OSs from Abca4−/− mice (Radu et al., 2011, 2014)”

What the sources say

• Not checked yetcites Radu et al., 2011 source
• Not checked yetcites Radu et al., 2014 source

In the paper

“With this phagocytic function, the RPE is responsible for the catabolic phase of the turnover of phototransductive membrane.”

In the paper

“In the early 1960s, Dowling and co-workers reported electron microscope (EM) images of what we now know as phagosomes containing packets of OS disk membranes in sections of rat RPE (Dowling and Gibbons, 1962) (Fig. 6A–C).”

What the sources say

• Not checked yetcites Dowling and Gibbons, 1962

In the paper

“LaVail (1976) first reported a greater number of phagosomes in the rat RPE after light onset.”

What the sources say

• Not checked yetcites LaVail, 1976 source

In the paper

“and iPS-RPE from patients with different monogenic forms of macular degeneration were observed to accumulate drusen deposits after 90 days of culture (Galloway et al., 2017).”

What the sources say

• Not checked yetcites Galloway et al., 2017 source

In the paper

“As discussed above, there are now reproducible protocols that generate RPE monolayers with a well-differentiated phenotype, not only for primary RPE cultures (Gibbs and Williams, 2003; Maminishkis et al., 2006; Strunnikova et al., 2010; Blenkinsop et al., 2013; Toops et al., 2014) and RPE cells derived from stem cells (Idelson et al., 2009; Buchholz et al., 2013; Gong et al., 2015; Maruotti et al.”

What the sources say

• Not checked yetcites Gibbs and Williams, 2003
• Not checked yetcites Maminishkis et al., 2006 source
• Not checked yetcites Strunnikova et al., 2010 source

In the paper

“An important part of the protocol, reported by Hazim et al. for ARPE-19 cells, is a series of washes with trypsin that selectively removes the more proliferative cells, which tend to be more loosely adhered to the substrate, leaving behind firmly attached cells that more readily form a culture with a cobblestone appearance (Hazim et al., 2019).”

What the sources say

• Not checked yetcites Hazim et al., 2019 source

In the paper

“In particular, human iPS-RPE cells offer the ability to develop ‘disease-in-a-dish’ models by obtaining iPSCs from patients with an inherited RPE pathology.”

In the paper

“Until recently, methods routinely used for culturing RPE cell lines yielded cultures that did not exhibit critical features characteristic of the RPE in vivo.”

In the paper

“The definitive demonstration that the RPE phagocytosed outer segment disks was not reported until 1969, when Young and Bok (1969) used microscopic autoradiography to trace radiolabeled disk membranes to phagosomes in the RPE (Fig. 6D).”

What the sources say

• Not checked yetcites Young and Bok, 1969

In the paper

“That defective phagocytic function of the RPE underlaid the retinal dystrophy of the RCS rat was subsequently resolved following an autoradiographic study (Bok and Hall, 1971), and observations of chimeric rats, generated to contain photoreceptor and RPE layers that consisted of mosaics of RCS and normal cells (Mullen and LaVail, 1976).”

What the sources say

• Not checked yetcites Bok and Hall, 1971
• Not checked yetcites Mullen and LaVail, 1976

In the paper

“In an example from retinal research, the rat retinal ganglion cell (RGC)-5 cell line had been used as a model for retinal ganglion cells. However, this line was somehow replaced by cells from a line of mouse cells (Krishnamoorthy et al., 2013), sharing some properties with the 661W cell line, which expresses several markers of mouse cone photoreceptors (Tan et al., 2004).”

What the sources say

• Not checked yetcites Krishnamoorthy et al., 2013 source
• Not checked yetcites Tan et al., 2004 source

In the paper

“Importantly, they do not exhibit essential polarity features that are characteristic of RPE, such as the specific apical localization of Na+/K+-ATPase and neural cell adhesion molecule (NCAM) (Nabi et al., 1993), which are critical for RPE and photoreceptor function.”

What the sources say

• Not checked yetcites Nabi et al., 1993 source

In the paper

“More recent work, however, has reported comparable phagosome numbers occurring at two peaks in the mouse and zebrafish RPE, with one peak after light onset and the other after lights-off (Lewis et al., 2018).”

What the sources say

• Not checked yetcites Lewis et al., 2018 source

In the paper

“Typically, the catabolic phase is initiated by endocytosis of the base of a microvillus, resulting in vesicles that aggregate in multivesicular bodies within the photoreceptor cell (Eguchi and Waterman, 1976; Satoh and Ready, 2005).”

What the sources say

• Not checked yetcites Eguchi and Waterman, 1976
• Not checked yetcites Satoh and Ready, 2005

In the paper

“a well polarized RPE cell possesses vertical microtubules that do not emanate from the centrosome”

In the paper

“ARPE-19 and primary RPE cells have been shown to ingest OSs in less than 1 h (Gibbs et al., 2003; Damek-Poprawa et al., 2009; Olchawa et al., 2013; Wavre-Shapton et al., 2014)”

What the sources say

• Not checked yetcites Gibbs et al., 2003
• Not checked yetcites Damek-Poprawa et al., 2009 source
• Not checked yetcites Olchawa et al., 2013 source

In the paper

“This method provides much better temporal resolution of ingestion and phagosome maturation than that available by in vivo analysis.”

In the paper

“In the central human retina, there are 33 photoreceptors associated with each RPE cell (Osterberg, 1935), and, in the center of a mouse retina, there are more than 200 photoreceptors for every RPE cell (Volland et al., 2015); the ratio decreases to ~12 in the periphery of the human retina and 100–120 in the periphery of a mouse retina (Volland et al., 2015).”

What the sources say

• Not checked yetcites Osterberg, 1935

In the paper

“- Externally-exposed phosphatidylserine at the OS tips and αvβ5 integrin in the RPE apical membrane facilitate OS binding to the RPE apical membrane.”

In the paper

“In dipterans, where the individual rhabdomeres are separated (to form an open rhabdom), the tips of the microvilli may be phagocytosed by adjacent regions of the photoreceptor cells (Williams, 1982c), in addition to endocytosis of the microvillar bases.”

What the sources say

• Not checked yetcites Williams, 1982c

In the paper

“the tips of OSs were found to contain PS exposed to the extracellular space, especially at light onset, using the PS-specific dye, pSIVA, a “polarity-sensitive indicator of viability and apoptosis” (Ruggiero et al., 2012)”

What the sources say

• Not checked yetcites Ruggiero et al., 2012 source

In the paper

“Although an auxiliary cell type is not commonly involved in the degradation of shed rhabdomeral membrane, there is evidence from spider retinas that the tips of the microvilli are ingested by adjacent, non-pigmented glia (Blest and Maples, 1979), thus representing an event that is more akin to ingestion of OS membranes by the RPE.”

What the sources say

• Not checked yetcites Blest and Maples, 1979

In the paper

“PS is concentrated in the cytoplasmic leaflet of OS membranes, due to the activity of PS flippases.”

In the paper

“latex beads, while used extensively in phagocytosis studies of other systems (Desjardins and Griffiths, 2003), have been shown to use molecular mechanisms, involved in binding and ingestion by RPE cell cultures, that are distinct from those used by the RPE for OS phagocytosis (Edwards and Szamier, 1977; Chaitin and Hall, 1983a; Finnemann et al., 1997).”

What the sources say

• Not checked yetcites Edwards and Szamier, 1977
• Not checked yetcites Chaitin and Hall, 1983a
• Not checked yetcites Finnemann et al., 1997

In the paper

“Importantly, however, maturation kinetics of OS phagosomes in well-differentiated RPE cell cultures, including cultures of primary RPE, human iPS-RPE, and ARPE-19 cells (Diemer et al., 2008; Hazim et al., 2017, 2019), is comparable to that in vivo.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Diemer et al., 2008
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Hazim et al., 2017, 2019

In the paper

“While this report suggests reasons for the differences in their study compared with previous studies, including mouse strain or species differences, the authors also discuss the obvious, though previously neglected issue that phagosome number is the net result of not just phagocytosis, but also the rate of phagosome degradation.”

In the paper

“the rate of phagosome degradation is affected by motility along the RPE cell microtubules (Jiang et al., 2015)”

What the sources say

• Not checked yetcites Jiang et al., 2015 source

In the paper

“Still, among different types of cultures, there is a large variation in the pulse time required for cells to achieve significant ingestion of OSs.”

In the paper

“Therefore, disk membrane proteins cannot be considered to have short lives.”

In the paper

“Studies on Drosophila have shown that degradation also includes classical autophagy (Midorikawa et al., 2010).”

What the sources say

• Not checked yetcites Midorikawa et al., 2010 source

In the paper

“Phagocytosis is a key function of the RPE that is significantly affected by RPE cell polarization.”

In the paper

“due to their fresh dissection, reflect the in vivo circadian rhythm of OS phagocytosis (LaVail, 1976)”

What the sources say

• Not checked yetcites LaVail, 1976 source

In the paper

“and are all important for the mechanisms and especially the kinetics of OS ingestion and degradation.”

In the paper

“A recent study has shown that the content of an OS phagosome influences its rate of degradation (Esteve-Rudd et al., 2018)”

What the sources say

• Not checked yetcites Esteve-Rudd et al., 2018 source

In the paper

“MERTK activation requires ligand binding of growth arrest-specific protein 6 (Gas6) or Protein S, which form the bridge between the RPE and exposed PS on OS.”

In the paper

“Aside from MERTK, there are data to suggest that other TAM receptors, such as TYRO3, and the lipid scavenger receptor CD36, both of which are expressed in the RPE (Ryeom et al., 1996; Prasad et al., 2006), may play a supporting role in OS phagocytosis.”

What the sources say

• Not checked yetcites Ryeom et al., 1996 source
• Not checked yetcites Prasad et al., 2006 source

In the paper

“OS binding requires the formation of a complex between the tetraspanin CD81 and αvβ5 (Chang and Finnemann, 2007).”

What the sources say

• Not checked yetcites Chang and Finnemann, 2007

In the paper

“More recently, it was noted that adenoviral TYRO3 transduction induced OS phagocytosis in Mertk−/−;Tyro3−/− primary mouse RPE, although to a lesser extent than adenoviral MERTK transduction (Vollrath et al., 2015).”

What the sources say

• Not checked yetcites Vollrath et al., 2015 source

In the paper

“Similar to MERTK, TYRO3 localizes to nascent phagosomes but not maturing ones (Feng et al., 2002).”

What the sources say

• Not checked yetcites Feng et al., 2002 source

In the paper

“The RCS rat also demonstrated that, unlike OS ingestion, MERTK was not required for latex bead ingestion (Edwards and Szamier, 1977).”

What the sources say

• Not checked yetcites Edwards and Szamier, 1977

In the paper

“Negative regulation of OS binding via αvβ5 integrin likely maintains the acute phagocytic burst in the RPE.”

In the paper

“Perhaps surprisingly, MFGE8, as the bridging molecule linking αvβ5 to the OS, plays only a minor role in retinal adhesion (Nandrot et al., 2007).”

What the sources say

• Not checked yetcites Nandrot et al., 2007 source

In the paper

“Indeed, β5−/− mice do not exhibit the characteristic peak of tyrosine phosphorylation seen in MERTK after light onset (Nandrot et al., 2004).”

What the sources say

• Not checked yetcites Nandrot et al., 2004 source

In the paper

“Similarly, determination of the size of the phagocytic cup, and the size of the ensuing phagosome is likely to involve an interaction between the pseudopodia and regulated features of the OS, such as PS exposure (see section 3.4 (Ruggiero et al., 2012);) or the presence of open OS disks (Matsumoto and Besharse, 1985).”

What the sources say

• Not checked yetcites Ruggiero et al., 2012 source
• Not checked yetcites Matsumoto and Besharse, 1985

In the paper

“Indeed, wild type primary rat RPE cells do not exhibit the characteristic increase in IP3 levels upon latex bead phagocytic challenge (Heth et al., 1995).”

What the sources say

• Not checked yetcites Heth et al., 1995

In the paper

“αvβ5 has also been implicated in mediating retinal adhesion to the RPE, typically assessed by measuring the partitioning of apical melanosome-containing microvilli with the sensory retina following mechanical separation of the RPE and retina.”

In the paper

“OS ingestion is mediated by rearrangement of the actin cytoskeleton to form an actin-rich phagocytic cup, first seen in early EM images of pseudopodia that were distinct from apical microvilli but in close apposition to the OS membrane (Steinberg et al., 1977; Nilsson, 1978; Matsumoto et al., 1987).”

What the sources say

• Not checked yetcites Steinberg et al., 1977 source
• Not checked yetcites Nilsson, 1978 source
• Not checked yetcites Matsumoto et al., 1987 source

In the paper

“Focal adhesion kinase (FAK) appears to be the bridging step between OS recognition by αvβ5 integrin and OS engulfment mediated by MERTK (Finnemann, 2003).”

What the sources say

• Not checked yetcites Finnemann, 2003 source

In the paper

“Lysosome involvement in phagosome degradation in the RPE was first noted by EM studies that identified acid phosphatase activity in both lysosomes and OS phagosomes (Ishikawa and Yamada, 1970).”

What the sources say

• Not checked yetcites Ishikawa and Yamada, 1970

In the paper

“To date, only myosin-2 has been shown to be necessary for OS ingestion in RPE (Strick et al., 2009).”

What the sources say

• Not checked yetcites Strick et al., 2009 source

In the paper

“The bidirectionality likely enhances encounters with endolysosomes (see next subsection).”

In the paper

“Moreover, these organelles could be seen in close apposition or fused to each other (Herman and Steinberg, 1982a).”

What the sources say

• Not checked yetcites Herman and Steinberg, 1982a

In the paper

“Herman and Steinberg found that, in the opossum RPE, the majority of phagosomes were located basally 1–2 h after light onset, with few remaining in the apical domain (Herman and Steinberg, 1982b).”

What the sources say

• Not checked yetcites Herman and Steinberg, 1982b

In the paper

“Similar treatments in albino rats prevented phagosome interactions with lysosomes, and thus acquisition of lysosomal acid phosphatase by the phagosomes (Beauchemin and Leuenberger, 1977).”

What the sources say

• Not checked yetcites Beauchemin and Leuenberger, 1977

In the paper

“ANXA2 likely functions upstream of FAK, as Anxa2−/− mice show delayed FAK phosphorylation following light onset.”

In the paper

“This translocation appeared to require the RPE microtubule cytoskeleton, as intravitreal injections of colchicine, an inhibitor of microtubule polymerization, caused phagosomes to accumulate in the apical RPE.”

In the paper

“RPE cells, differentiated from human adult RPE stem cells, that still had actin stress fibers, despite having junctional ZO-1 labeling and comparable apical expression of the αvβ5 integrin, exhibited a lower phagocytic capacity compared with more polarized cells, containing circumferential actin at the level of the junctional complexes and actin filaments within apical processes (Müller et al., 20”

What the sources say

• Not checked yetcites Müller et al., 2018 source

In the paper

“This evidence indicates that OS disk shedding and phagocytosis are not separate events, and, although the term, “disk shedding”, has been used historically, it is misleading and its use should probably be avoided in the context of OS disk membrane renewal.”

In the paper

“Treatment of differentiated ARPE-19 cells with ANXA2 siRNA leads to decreased ingestion (but not binding) of OS.”

In the paper

“It seems likely that this deficiency in myosin-7a activity may contribute to the inherited blindness in Usher syndrome type 1B, which is caused by mutations in the human orthologue, MYO7A (Weil et al., 1995).”

What the sources say

• Not checked yetcites Weil et al., 1995 source

In the paper

“Their observation meant that, shortly after OS membrane ingestion, the resulting phagosomes had translocated ~100 μm, the distance between the apical and basal domains of the opossum RPE.”

In the paper

“As early as Young and Bok’s paper on OS phagocytosis (Young and Bok, 1969), it was known that, once ingested, phagosomes traverse the RPE from the apical to basolateral domain, where they are ‘eliminated’.”

What the sources say

• Not checked yetcites Young and Bok, 1969

In the paper

“Imaging of OS phagosomes in live primary RPE cells showed that the phagosomes undergo rapid back and forth movements along labeled microtubules (see Video 2 in Jiang et al., 2015).”

What the sources say

• Not checked yetcites Jiang et al., 2015 source

In the paper

“Given the importance of actin in phagocytosis, the polarity of the actin cytoskeleton can act as an indicator of RPE phagocytic capacity.”

In the paper

“Both myosin-7a and myosin-6 have been reported to colocalize with OS phagosomes in the RPE (Jiang et al., 2015; Yu et al., 2018).”

What the sources say

• Not checked yetcites Jiang et al., 2015 source
• Not checked yetcites Yu et al., 2018

In the paper

“- Proteins, such as RAB5 and RAB7, associate with phagosomes at different stages, thus marking as well as functioning in different stages of phagosome maturation.”

In the paper

“The external PS localization at the tips of OSs, mentioned above, is stimulated only in the presence of the RPE, since it requires the RPE integrin, αvβ5, and its extracellular ligand, MFGE8 (Ruggiero et al., 2012).”

What the sources say

• Not checked yetcites Ruggiero et al., 2012 source

In the paper

“Moreover, despite being a downstream effector of PI3K, AKT functions independently from PI3K during phagocytosis (Bulloj et al., 2013).”

What the sources say

• Not checked yetcites Bulloj et al., 2013 source

In the paper

“Prior to association with the microtubule cytoskeleton, phagosomes must first pass through the apical actin meshwork of the RPE.”

In the paper

“Myosin-6 downregulation was also shown to delay phagosome clearance (Yu et al., 2018).”

What the sources say

• Not checked yetcites Yu et al., 2018

In the paper

“By immunoEM of RPE sections, OS phagosome acidification and cathepsin D acquisition occur concurrently with the loss of opsin antigenicity (Deguchi et al., 1994).”

What the sources say

• Not checked yetcites Deguchi et al., 1994

In the paper

“They also display delayed phagosome degradation, both in vivo and in vitro, increased laminin deposition in Bruch’s membrane, and greater accumulation of bisretinoids such as A2E in aged Mreg−/− mice compared to age-matched controls.”

In the paper

“RPE from Mreg−/− mice have decreased levels of the mature enzyme (Damek-Poprawa et al., 2009), and increased secretion of pro-cathepsin D into the extracellular medium (Frost et al., 2013).”

What the sources say

• Not checked yetcites Damek-Poprawa et al., 2009 source

In the paper

“Alterations in phagosome content itself may also affect phagosome association with RAB proteins.”

In the paper

“Cathepsin D maturation (Hoppe et al., 2004a), but not expression, is impaired in RPE cells treated with oxidized LDL, thereby leading to inefficient OS phagosome degradation (Hoppe et al., 2001).”

What the sources say

• Not checked yetcites Hoppe et al., 2004a

In the paper

“The incomplete maturation or mistargeting of cathepsin D is associated with perturbations in phagosome degradation.”

In the paper

“Defects in lysosomal acidification through chronic administration of lysosomal alkalinizing agents result in extrusion of undigested OS phagocytic material from the basal RPE into the space between Bruch’s membrane and the RPE (Peters et al., 2006).”

What the sources say

• Not checked yetcites Peters et al., 2006 source

In the paper

“These cells also demonstrated increased secretion of the pro-enzyme into the extracellular space.”

In the paper

“Cathepsin D maturation (Hoppe et al., 2004a), but not expression, is impaired in RPE cells treated with oxidized LDL, thereby leading to inefficient OS phagosome degradation (Hoppe et al., 2001).”

What the sources say

• Not checked yetcites Hoppe et al., 2004a

In the paper

“Furthermore, pharmacological re-acidification of ARPE-19 cells, pretreated with lysosomal alkalinizing agents, increases their ability to degrade OS by reestablishing an acidic lysosomal environment more conducive to efficient protease activity (Liu et al., 2008).”

What the sources say

• Not checked yetcites Liu et al., 2008 source

In the paper

“While the molecular implications of the association of these markers are not well understood, the change in marker association indicates the presence of different stages in OS phagosome maturity.”

In the paper

“Similarly, melanoregulin (MREG), a small, highly-charged protein that localizes to lysosomes (Frost et al., 2013), is important for cathepsin D maturation.”

What the sources say

• Not checked yetcites Frost et al., 2013 source

In the paper

“Endolysosomal acidification is thought to be regulated by direct interaction of βA3/A1-crystallin with lysosomal v-ATPase (Valapala et al., 2014).”

What the sources say

• Not checked yetcites Valapala et al., 2014 source

In the paper

“Choroideremia is caused by mutations in the REP1 (aka CHM) gene, which encodes RAB escort protein-1 (Cremers et al., 1990; Seabra et al., 1992).”

What the sources say

• Not checked yetcites Cremers et al., 1990 source
• Not checked yetcites Seabra et al., 1992 source

In the paper

“Moreover, it suggests a stepwise role for different endolysosomes in OS phagosome maturation.”

In the paper

“Colocalization of OS phagosomes with these endolysosomal markers has suggested a trend such that early phagosomes associate with early endosome markers, RAB5 and EEA1, but this association wanes as LAMP1/2 association rises (Yu et al., 2018).”

What the sources say

• Not checked yetcites Yu et al., 2018

In the paper

“It was reported to degrade OS proteins in vitro (Hayasaka et al., 1975; Rakoczy et al., 1997), including rhodopsin (Regan et al., 1980).”

What the sources say

• Not checked yetcites Hayasaka et al., 1975 source
• Not checked yetcites Rakoczy et al., 1997 source
• Not checked yetcites Regan et al., 1980 source

In the paper

“The presence of cathepsin D multimers, i.e., 46–60 kDa minimally active enzyme forms, in primary human RPE cultures correlate with the accumulation of autofluorescent debris derived from prolonged OS feeding (Rakoczy et al., 1996), suggesting a reduction in the degradative capacity of the culture.”

What the sources say

• Not checked yetcites Rakoczy et al., 1996 source

In the paper

“Perhaps, unsurprisingly, there is strict regulation of cathepsin D activity using post-translational modifications (Lai et al., 2000).”

What the sources say

• Not checked yetcites Lai et al., 2000 source

In the paper

“RPE from Mreg−/− mice have decreased levels of the mature enzyme (Damek-Poprawa et al., 2009), and increased secretion of pro-cathepsin D into the extracellular medium (Frost et al., 2013).”

What the sources say

• Not checked yetcites Frost et al., 2013 source

In the paper

“REPs are involved in RAB prenylation, a lipid modification that allows RAB membrane binding and function, and thus the association of RAB proteins with specific organelles.”

In the paper

“Rep1 knockout mice demonstrate delayed in vivo phagosome degradation (Wavre-Shapton et al., 2013).”

What the sources say

• Not checked yetcites Wavre-Shapton et al., 2013

In the paper

“The presence of cathepsin D multimers, i.e., 46–60 kDa minimally active enzyme forms, in primary human RPE cultures correlate with the accumulation of autofluorescent debris derived from prolonged OS feeding (Rakoczy et al., 1996), suggesting a reduction in the degradative capacity of the culture.”

What the sources say

• Not checked yetcites Rakoczy et al., 1996 source

In the paper

“However, in recent years, emerging evidence, particularly from immunodetection of rhodopsin, suggests that phagosome maturation is likely more complex and proceeds in stages.”

In the paper

“In contrast, monoclonal antibodies, 4D2 and RET-P1, raised against the rod opsin N-terminus, labeled both mature and early phagosomes.”

In the paper

“Cathepsin D maturation (Hoppe et al., 2004a), but not expression, is impaired in RPE cells treated with oxidized LDL, thereby leading to inefficient OS phagosome degradation (Hoppe et al., 2001).”

What the sources say

• Not checked yetcites Hoppe et al., 2001

In the paper

“The importance of cathepsin D is well illustrated by the mcd/mcd transgenic mouse model which expresses a mutated form of cathepsin D rendering it enzymatically inactive (Rakoczy et al., 2002).”

What the sources say

• Not checked yetcites Rakoczy et al., 2002 source

In the paper

“One of the hallmarks of a maturing phagosome is increasing acidification.”