2013
DOI: 10.1016/j.cell.2013.06.012
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Noncanonical Autophagy Promotes the Visual Cycle

Abstract: SUMMARY Phagocytosis and degradation of photoreceptor outer segments (POS) by the retinal pigment epithelium (RPE) is fundamental to vision. Autophagy is also responsible for bulk degradation of cellular components but its role in POS degradation is not well understood. We report that the morning burst of RPE phagocytosis coincided with the enzymatic conversion of autophagy protein LC3 to its lipidated form. LC3 then associated with single membrane phagosomes containing engulfed POS in an Atg5 dependent manner… Show more

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Cited by 308 publications
(293 citation statements)
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“…13,14,[28][29][30][31] Recent studies from our laboratory and others indicate a potential role of autophagy either pretreated or not treated with rapamycin (100 nM) for 3 h. Data were analyzed using oneway ANOVA and differences between means were considered statistically significant when P < 0.05. in lipofuscin accumulation, drusen formation, and AMD pathogenesis. 14,22,31 We found that with aging there seemed to be a dramatic increase in LC3, ATG7, and ATG9 in the RPE as well as other retinal layers of non-AMD human donors and our rodent models.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…13,14,[28][29][30][31] Recent studies from our laboratory and others indicate a potential role of autophagy either pretreated or not treated with rapamycin (100 nM) for 3 h. Data were analyzed using oneway ANOVA and differences between means were considered statistically significant when P < 0.05. in lipofuscin accumulation, drusen formation, and AMD pathogenesis. 14,22,31 We found that with aging there seemed to be a dramatic increase in LC3, ATG7, and ATG9 in the RPE as well as other retinal layers of non-AMD human donors and our rodent models.…”
Section: Discussionmentioning
confidence: 99%
“…6 A number of studies have reported that autophagy occurs in the RPE. [13][14][15][16] However, insufficient digestion due to impaired autophagy or lysosomal degradation in the RPE is reported to lead to an accumulation of damaged organelles, toxic proteins including lipofuscin, and extracellular drusen deposits, all of which can contribute to RPE dysfunction or death and have been associated with the pathogenesis of AMD. 7,10,17 To better understand the role of the autophagy-lysosome pathway for RPE homeostasis, aging, and AMD, we studied the autophagic process and the cellular and molecular pathways under oxidative stress.…”
Section: Introductionmentioning
confidence: 99%
“…Previously LAP was shown to be required for retinoid recycling by phagocytic retinal pigment epithelial cells, which contributes to maintaining vision in mice [10], and LAP-like LC3 lipidation also occurs on macropinosomes [5], and at the ruffled border in osteoclasts [11], suggesting that LAP may contribute significantly to physiology in multiple contexts. In their study, Martinez and colleagues leveraged previous work identifying numerous genes required for LAP versus autophagy to build, by correlation, a compelling model of LAP function in vivo [5][6][7].…”
mentioning
confidence: 99%
“…16 Autophagy has a cytoprotective role in retinal ganglion cells (RGCs) after optic nerve axotomy, 17,18 while autophagy has a detrimental effect on crush-induced acute axonal degeneration of the optic nerve. 19 The role of autophagy in maintaining photoreceptors remains largely unknown.…”
Section: Introductionmentioning
confidence: 99%