title: Noncanonical autophagy promotes the visual cycle.
abstract: Phagocytosis and degradation of photoreceptor outer segments (POS) by 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 associated with single-membrane phagosomes containing engulfed POS in an Atg5-dependent manner that required Beclin1, but not the autophagy preinitiation complex. The importance of this process was verified in mice with Atg5-deficient RPE cells that showed evidence of disrupted lysosomal processing. These mice also exhibited decreased photoreceptor responses to light stimuli and decreased chromophore levels that were restored with exogenous retinoid supplementation. These results establish that the interplay of phagocytosis and autophagy within the RPE is required for both POS degradation and the maintenance of retinoid levels to support vision.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University, St. Louis School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Jennifer
authors.initials: J
authors.lastname: Martinez
authors.forename: Teresa Ann
authors.initials: TA
authors.lastname: Doggett
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kolesnikov
authors.forename: Peter H
authors.initials: PH
authors.lastname: Tang
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Ablonczy
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Zhou
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Green
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Ferguson
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; D002417:Cattle; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism; D014785:Vision, Ocular
chemical_list: D051017:Apoptosis Regulatory Proteins; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; C115010:Becn1 protein, mouse; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D012176:Retinoids