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Cited by 130Retinal Diseases and TreatmentsAutophagy in Disease and TherapyRetinal Development and Disorders

Deletion of autophagy inducer RB1CC1 results in degeneration of the retinal pigment epithelium

Open access
Yao, Jingyu, Jia, Lin, Khan, Naheed, Lin, Chengmao, Mitter, Sayak K, Boulton, Michael E, Dunaief, Joshua L, Klionsky, Daniel J +3 more·2015·Autophagy
DOI 10.1080/15548627.2015.1041699PMC PMC4502815
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Abstract

Autophagy regulates cellular homeostasis and response to environmental stress. Within the retinal pigment epithelium (RPE) of the eye, the level of autophagy can change with both age and disease. The purpose of this study is to determine the relationship between reduced autophagy and age-related degeneration of the RPE. The gene encoding RB1CC1/FIP200 (RB1-inducible coiled-coil 1), a protein essential for induction of autophagy, was selectively knocked out in the RPE by crossing Best1-Cre mice with mice in which the Rb1cc1 gene was flanked with Lox-P sites (Rb1cc1(flox/flox)). Ex vivo and in vivo analyses, including western blot, immunohistochemistry, transmission electron microscopy, fundus photography, optical coherence tomography, fluorescein angiography, and electroretinography were performed to assess the structure and function of the retina as a function of age. Deletion of Rb1cc1 resulted in multiple autophagy defects within the RPE including decreased conversion of LC3-I to LC3-II, accumulation of autophagy-targeted precursors, and increased numbers of mitochondria. Age-dependent degeneration of the RPE occurred, with formation of atrophic patches, subretinal migration of activated microglial cells, subRPE deposition of inflammatory and oxidatively damaged proteins, subretinal drusenoid deposits, and occasional foci of choroidal neovascularization. There was secondary loss of photoreceptors overlying the degenerated RPE and reduction in the electroretinogram. These observations are consistent with a critical role of autophagy in the maintenance of normal homeostasis in the aging RPE, and indicate that disruption of autophagy leads to retinal phenotypes associated with age-related degeneration.

AI snapshot

Written from the paper’s full text.

TL;DR

RPE-specific deletion of the autophagy inducer RB1CC1 in mice causes progressive, age-dependent retinal pigment epithelium degeneration with AMD-like features and secondary photoreceptor loss. The findings support a critical role for canonical macroautophagy in maintaining RPE homeostasis.

Key findings

  • Conditional Rb1cc1 knockout in mouse RPE reduced autophagy: decreased LC3-I to LC3-II conversion, increased SQSTM1/p62, accumulation of unprocessed phagosomes, and increased mitochondria; the overlying retina had normal RB1CC1 and equal LC3-I to LC3-II conversion.
  • The RPE phenotype was age-dependent: at 2 mo Rb1cc1-CKO retinas were similar to controls by OCT/histology and ERG; at 4 mo there were small white-yellowish structures, patchy RPE atrophy, hyperreflective subretinal spots, and CD68-positive macrophage infiltration; by 8 mo there was widespread RPE disruption, vacuolization, atrophy, TJP1/ZO-1 disorganization, and increased IBA1-positive cells.
  • Rb1cc1-CKO RPE showed AMD-like changes: Bruch’s membrane disruption by CD29 staining, subRPE C3 and nitrotyrosine deposition, increased autofluorescence/lipofuscin, Oil Red O lipid accumulation, SQSTM1/ubiquitin-tagged debris, and occasional histologic choroidal neovascularization.
  • Secondary photoreceptor degeneration occurred despite normal photoreceptor autophagy markers: decreased outer nuclear layer thickness and progressive age-dependent reductions in photopic and scotopic ERG responses.

Methods

  • ARPE-19 cells: siRNA knockdown of RB1CC1, photoreceptor outer segment feeding, bafilomycin A1 treatment, western blot, and immunofluorescence for LC3/SQSTM1.
  • Mice: RPE-specific Rb1cc1-CKO generated by crossing Best1-Cre with Rb1cc1 flox/flox; controls were Rb1cc1 wt; Best1-Cre littermates. Analyzed at 2, 4, and 8 mo by western blot, immunohistochemistry, transmission electron microscopy, fundus photography, OCT, fluorescein angiography, ERG, RPE flat mounts, Oil Red O, and autofluorescence.
  • Statistics: mean ± SD; two-tailed Student t test and one-way ANOVA with Bonferroni correction; Kruskal-Wallis for western blotting; significance at P < 0.05.

Limitations

  • Stated: the authors cannot conclude that decreased autophagy is the primary cause of AMD; the data support dysregulation of this pathway as critical but not primary.
  • Stated: they cannot definitively state that the observed vessels are of choroidal origin; neovascularization foci were infrequent, seen only on histology, with no significant hyperfluorescence on angiography.
  • Stated: the data do not address the role of LC3-associated phagocytosis in processing shed outer segments. Evident: findings are from a mouse model and ARPE-19 cells, so human AMD relevance remains inferential.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1080/15548627.2015.1041699

Cites

78 of 78 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 11 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Rb1cc1-CKO mice have decreased levels of lysosome markers mature CTSD/cathepsin D and LAMP1, consistent with defective processing of intracellular debris.

    “There were decreased levels of lysosome markers, such as mature CTSD/cathepsin D and LAMP1 (Fig. 9), consistent with defective processing of intracellular debris.”
    Quote in the paperSubstantial claim
  • Findingown data

    In RPE from Rb1cc1-CKO and control mice, levels of phosphorylated PTK2, phosphorylated MAPK8/9, total PTK2, and total MAPK8/9 are comparable.

    “We found comparable levels of phosphorylated-PTK2 (pPTK2) and phosphorylated-MAPK8/JNK1-MAPK9/JNK2 (pMAPK8/9), as well as the levels of total PTK2 and MAPK8/9, in the RPE from both experimental and littermate control mice (Fig. 2D andF).”
    Quote in the paperSubstantial claim
  • Findingown data

    Disruption of Bruch's membrane in Rb1cc1-CKO cells is demonstrated by staining for CD29.

    “Disruption of Bruch's membrane in the Rb1cc1-CKO cells was demonstrated by staining for CD29, a component of the ITGB1/integrin b-1 complex that localizes to the basal surface of the RPE and that serves as a surrogate marker for disruption of the Bruch's-RPE interface and integrity of this structure (Fig. 6A andB).”
    Quote in the paperSubstantial claim
  • Findingown data

    The neutral lipid accumulations in Rb1cc1-CKO RPE localize primarily to the basal aspect of the RPE.

    “These accumulations localized primarily to the basal aspect of the RPE.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Transmission electron microscopy shows increased accumulation of single-membrane phagosome-like structures in Rb1cc1-CKO cells.

    “Finally, transmission electron microscopy showed increased accumulation of single-membrane phagosomelike structures in the Rb1cc1-CKO cells (Fig. 4I-K).”
    Quote in the paperSubstantial claim
  • May combine two claims. 25
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 9

  • May combine two claims.

    Findingown data

    In ARPE-19 cells, RB1CC1 siRNA treatment significantly reduces the punctate pattern of LC3 staining, consistent with formation of fewer autophagosomes.

    “Immunofluorescence analysis showed RB1CC1 siRNA-treated ARPE-19 cells have a significantly reduced punctate pattern of LC3 staining (green), consistent with the formation of fewer autophagosomes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There is accumulation of oxidatively damaged proteins on the basal surface of the RPE in Rb1cc1-CKO mice, with a resultant inflammatory response, demonstrated by nitrotyrosine and C3 staining.

    “There was an accumulation of oxidatively damaged proteins on the basal surface of the RPE, with a resultant inflammatory response, as demonstrated by the presence of nitrotyrosine-positive staining and C3 (complement component 3) staining, respectively (Fig. 7A-D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Rb1cc1-CKO mice show increased presence of IBA1-positive cells even at 8 months of age, consistent with activation of an immunological response to RPE degeneration.

    “we detected an increased presence of IBA1-positive cells in the Rb1cc1-CKO mice even at 8 mo of age (Fig. 5G); IBA1 being a marker of activated microglial cells and consistent with the activation of an immunological response to the RPE degeneration.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Rb1cc1-CKO mice show markedly increased autofluorescence in the RPE compared to control animals, most likely due to accumulation of lipofuscin.

    “We also observed markedly increased autofluorescence in the RPE of the Rb1cc1-CKO mice compared to the control animals, most likely due to accumulation of lipofuscin (Fig. 7E andF).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Rb1cc1-CKO retinas at 4 months show small white-yellowish structures and areas of patchy RPE atrophy.

    “Examination of the Rb1cc1-CKO retinas revealed small, whiteyellowish structures and areas of patchy RPE atrophy (Fig. 4A andB).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The neovascular foci in Rb1cc1-CKO mice are infrequently seen and only on histology.

    “These foci were infrequently seen, and only on histology.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At 2 months of age, the RPE of Rb1cc1-CKO mice is identical to littermate controls in RPE appearance and integrity of RPE65 staining.

    “The RPE of the Rb1cc1-CKO mice were identical to the littermate controls in terms of the RPE appearance and integrity of RPE65 staining (a RPE-specific marker indicative of normal RPE function; Fig. 3E andF).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In Rb1cc1-CKO mouse RPE, LC3-II levels are markedly reduced and SQSTM1 accumulates significantly, consistent with defective autophagy.

    “There was also a markedly reduced level of LC3-II and a significant accumulation of SQSTM1, both consistent with defective autophagy in the RPE (Fig. 2A andB).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Electron microscopy shows poorly processed phagosomes and accumulation of vacuoles, presumably lipid-filled, some large enough to force apical displacement of melanosomes.

    “Electron microscopy showed poorly processed phagosomes and accumulation of vacuoles, presumably lipid-filled and some large enough to force an apical displacement of the melanosomes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In Rb1cc1-CKO mice at 8 months, there are areas of RPE vacuolization and RPE atrophy with disorganization of the overlying retina.

    “There were areas of RPE vacuolization as well as areas of RPE atrophy, with disorganization of the overlying retina (Fig. 5C-E).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the overlying retina of Rb1cc1-CKO mice, RB1CC1 levels are normal and LC3-I to LC3-II conversion is equal to controls, consistent with cell-specific deletion.

    “In the overlying retina there were normal levels of RB1CC1 and equal conversion of LC3-I to LC3-II, consistent with the cell-specific nature of the autophagy gene deletion (Fig. 2D).”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    By 8 months of age, there is widespread disruption of RPE cell morphology and the overlying retina in Rb1cc1-CKO mice.

    “The abnormal phenotype increased in severity with increasing age, and by 8 mo there was widespread disruption of the RPE”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Inhibiting autophagosome-lysosome fusion with bafilomycin A1 increased LC3-II and SQSTM1 in control cells, ruling out lysosomal disruption as the cause of accumulation in the absence of bafilomycin A1.

    “Inhibiting autophagosome-lysosome fusion with bafilomycin A 1 showed an increase in LC3-II and SQSTM1 in the control cells, which rules out the possibility that the accumulation is due to lysosomal disruption in the absence of bafilomycin A 1 .”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Immunostaining for Cre-recombinase showed no RPE degeneration in Best1-Cre control retinas, but only in Rb1cc1-CKO retinas where there was Cre expression.

    “(G, H) Immunostaining for the Cre-recombinase (red) showed that there was no RPE degeneration in the Best1-Cre control retinas, but only in the Rb1cc1-CKO retinas where there was Cre expression.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In all cases, abnormalities were only seen in Rb1cc1-CKO mouse, and not in Best1-Cre mouse, even in areas of Cre expression.

    “In all cases, abnormalities were only seen in the Rb1cc1-CKO mouse, and not in the Best1-Cre mouse, even in areas of Cre expression.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    RB1CC1 is a component of the ULK1-ATG13-RB1CC1/FIP200 complex, which is inhibited by MTOR and is an essential upstream inducer of autophagy.

    “RB1CC1 is a component of the ULK1-ATG13-RB1CC1/FIP200 complex, which is inhibited by MTOR and is an essential upstream inducer of autophagy. [26][27]7][28][29]”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    RB1CC1 is also important in regulating intracellular signaling pathways such as cell survival, differentiation, migration, proliferation, and protein synthesis.

    “Aside from the essential function of RB1CC1 in regulating autophagy in mammalian cells, it is also important in regulating a number of intracellular signaling pathways such as cell survival, differentiation, migration, proliferation, and protein synthesis. 38”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The Rb1cc1-CKO model demonstrates that blocking induction of autophagy in the RPE results in many salient features of AMD, particularly RPE atrophy, accumulation of lipid-filled inclusions, drusenoid deposits, abnormal accumulation of reactive oxygen species, complement activation, and occasional foci of neovascularization.

    “The model presented here demonstrates that blocking the induction of autophagy in the RPE results in many of the salient features of AMD, particularly RPE atrophy, the accumulation of lipid-filled inclusions, drusenoid deposits, abnormal accumulation of reactive oxygen species, complement activation, and occasional foci of neovascularization.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Autophagy plays a critical role in lipid metabolism and reduces lipid toxicity in a number of animal models of disease.

    “Autophagy plays a critical role in lipid metabolism and reduces lipid toxicity in a number of animal models of disease. 68,69”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [68] source

      Not checked in the free run.

    • cites [69] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Markers of autophagy and exosomes have been found in the RPE of aged mice as well as in drusen from cadaveric eyes from people with age-related macular degeneration (AMD).

    “For example, markers of autophagy and exosomes have been found in the RPE of aged mice as well as in drusen from cadaveric eyes from people with age-related macular degeneration (AMD), 16”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Autophagy in the RPE is activated in a circadian rhythm, with a phase-shift of several hours relative to the peak of disc shedding.

    “We recently reported that autophagy in the RPE is activated in a circadian rhythm, 36 with a phase-shift of several hours relative to the peak of disc shedding, consistent with the time required for normal phagocytic processing of the outer segments.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    There appeared to be normal phagocytic ingestion of shed photoreceptor outer segments in Rb1cc1-CKO mice, suggesting that LC3-associated phagocytosis (LAP) was not affected.

    “There appeared to be normal phagocytic ingestion of the shed photoreceptor outer segments, suggesting that LAP was not affected.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Changes in RPE autophagy correlate with both progressive age and outer retinal degeneration.

    “Previous studies have shown that changes in RPE autophagy correlate with both progressive age and outer retinal degeneration. [16][17]7][18][19][20][21]”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Knocking down RB1CC1 in the RPE did not significantly affect nonautophagy-related RB1CC1 targets, consistent with a primarily autophagy defect rather than PTK2/MAPK pathway effects.

    “These results suggested that knocking down RB1CC1 expression in the RPE did not significantly affect the levels of nonautophagy-related RB1CC1 targets, and were consistent with the Rb1cc1-CKO having primarily a defect on autophagy and not on the PTK2 and MAPK pathways.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The RPE-specific defect in autophagy and resultant RPE degeneration causes a loss of photoreceptor cells; since autophagy in photoreceptors is normal, their death is secondary to the loss of the RPE.

    “The RPE-specific defect in autophagy and resultant RPE degeneration also causes a loss of photoreceptor cells.Since autophagy in the photoreceptors is normal in this model, presumably their death is secondary to the loss of the RPE.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The Best1 promoter provides RPE-specific expression of Cre-recombinase and RPE-selective loss of a loxP-flanked gene.

    “Recently, Dunaief and coworkers described a mouse strain in which the Best1 promoter was used to provide RPE-specific expression of the Crerecombinase and RPE-selective loss of a loxP-flanked gene. 34”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    All collections were performed at the same time of day (1:00 p.m.) because of circadian changes in autophagy levels in the RPE.

    “Due to the presence of circadian changes in autophagy levels in the RPE, 36 all collections were performed at the same time of day, 1:00 p.m.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Images in each individual experiment were acquired with a fixed detection gain.

    “All images in each individual experiment were acquired with a fixed detection gain.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Manual measurement of ONL thickness versus total retinal thickness confirmed the automated measurements.

    “(C) Manual measurement of the ONL thickness vs. total retinal thickness confirmed the automated measurements.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Mice negative for mutation in the Crb1/Rd8 gene were used.

    “All mice were genotyped by established methods and only those negative for mutation in the Crb1/Rd8 gene were used. 70”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [70] source

      Not checked in the free run.

30 of 30

  • The paper relies on this without support.

    Photoreceptors are highly dependent on the RPE for metabolic support.

    “This effect is not altogether unexpected, as the photoreceptors are highly dependent on the RPE for metabolic support.”
1 of 1

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?

  • Loss of RB1CC1 causes RPE atrophy and pigmentation defects as early as 4 months of age.

    “Loss of RB1CC1, a component of the ULK complex required to initiate autophagy, was shown to cause RPE atrophy and pigmentation defects as early as 4 months of age (Yao et al., 2015).”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Yao et al., 2015

  • Decreased autophagy led to a secondary degeneration of photoreceptors, loss of scotopic and photopic vision, subretinal inflammation, and sub-RPE accumulation of oxidative stress markers in 8-month-old mice.

    “Decreased autophagy led to a secondary degeneration of photoreceptors, loss of scotopic and photopic vision, subretinal inflammation (microglial activation, complement activation), and sub-RPE accumulation of oxidative stress markers in 8-month-old mice.”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Yao et al., 2015

  • This was accompanied by the accumulation of p62/SQSTM1, damaged mitochondria, and lipid droplets with increased autofluorescence in the RPE, all indicators of impaired autophagic flux.

    “This was accompanied by the accumulation of p62/SQSTM1, damaged mitochondria, and lipid droplets with increased autofluorescence in the RPE, all indicators of impaired autophagic flux.”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Yao et al., 2015

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.

  • Figure 6 panel F assigned two imaging methods

    Minor

    The Figure 6 caption identifies panel F as OCT imaging and also as IB4 staining.

  • Neovascularization described as visible only on histology and also on OCT

    Minor

    The results say the vascular-ingrowth foci were seen only on histology, but the Figure 6 caption says the finding was also seen on OCT.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 9

  1. Linsenmeier RA, 2000, Invest Ophthalmol Vis Sci, 41, 3117
  2. Reme CE, 1977, Invest. Ophthalmol Vis Sci, 16, 807
  3. Viiri J, 2010, Mol Vis, 16, 1399
  4. Mitter SK, Autophagy
  5. Zacks DN, 2002, Invest Ophthalmol Vis Sci, 43, 2384
  6. Zhao Y, 2014, Mol Neurobiol
  7. Mazzoni F, 2014, Exp Eye Res
  8. Gibbings D, 2013, Autophagy, 14, 1314
  9. Hemati N, 2005, Mol Vis, 11, 1151

Cited by

Sorted by citations

Related

Authors
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., & Zacks, D. N.
Affiliations
  • University of Michigan (US)
  • Indiana University School of Medicine (US)
  • University of Pennsylvania (US)
  • University of Cincinnati (US)
Corresponding author
Zacks, David N
ORCID
Venue
Autophagy
Publisher
Informa UK Limited
Published
2015-06-03
Volume
11
Issue
6
Pages
939-953
ISSN
  • 1554-8627 (ISSN-L)
  • 1554-8635
DOI
10.1080/15548627.2015.1041699
PMC
PMC4502815
OpenAlex
W1762842507
Semantic Scholar
07bce5549f84e5acb548a041638cd5c386e1a073
Cited by
130
References
78
Citations by year
2026: 4 · 2025: 21 · 2024: 9 · 2023: 10 · 2022: 11 · 2021: 12 · 2020: 17 · 2019: 12 · 2018: 11 · 2017: 9 · 2016: 10 · 2015: 4
FWCI
10.88
Type
journal article
Language
en
Open access
Locations
  • Autophagy (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Research to Prevent Blindness (EY007003)
  • Arnold and Mabel Beckman Initiative for Macular Research
  • National Eye Institute (R01EY020823, EY-020823, EY-007003, R01EY015240)
  • National Institute of General Medical Sciences (R01GM053396)
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
Keywords
RB1CC1, FIP200, retinal pigment epithelium, age-related degeneration, LC3 conversion, mitochondrial accumulation, microglial activation, drusen, choroidal neovascularization, photoreceptor loss, electroretinogram
MeSH terms
Autophagy-Related Proteins, Animals, Autophagy, Electroretinography, Epithelium, Mitochondria, Sequence Deletion, Intracellular Signaling Peptides and Proteins, Mice, Retinal Pigment Epithelium

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