title: Autophagy and heterophagy dysregulation leads to retinal pigment epithelium dysfunction and development of age-related macular degeneration.
abstract: Age-related macular degeneration (AMD) is a complex, degenerative and progressive eye disease that usually does not lead to complete blindness, but can result in severe loss of central vision. Risk factors for AMD include age, genetics, diet, smoking, oxidative stress and many cardiovascular-associated risk factors. Autophagy is a cellular housekeeping process that removes damaged organelles and protein aggregates, whereas heterophagy, in the case of the retinal pigment epithelium (RPE), is the phagocytosis of exogenous photoreceptor outer segments. Numerous studies have demonstrated that both autophagy and heterophagy are highly active in the RPE. To date, there is increasing evidence that constant oxidative stress impairs autophagy and heterophagy, as well as increases protein aggregation and causes inflammasome activation leading to the pathological phenotype of AMD. This review ties together these crucial pathological topics and reflects upon autophagy as a potential therapeutic target in AMD.
authors.affiliation: Department of Ophthalmology; Institute of Clinical Medicine; University of Eastern Finland; Kuopio, Finland; Department of Ophthalmology; Kuopio University Hospital; Kuopio, Finland.
authors.forename: Kai
authors.initials: K
authors.lastname: Kaarniranta
authors.forename: Debasish
authors.initials: D
authors.lastname: Sinha
authors.forename: Janusz
authors.initials: J
authors.lastname: Blasiak
authors.forename: Anu
authors.initials: A
authors.lastname: Kauppinen
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Veréb
authors.forename: Antero
authors.initials: A
authors.lastname: Salminen
authors.forename: Michael E
authors.initials: ME
authors.lastname: Boulton
authors.forename: Goran
authors.initials: G
authors.lastname: Petrovski
mesh_terms: D001343:Autophagy; D006801:Humans; D008247:Lysosomes / Q000473:pathology; D008268:Macular Degeneration / Q000473:pathology* / Q000503:physiopathology*; D010588:Phagosomes / Q000378:metabolism / Q000648:ultrastructure; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000473:pathology* / Q000503:physiopathology* / Q000648:ultrastructure
chemical_list: D046988:Proteasome Endopeptidase Complex
keywords: AMD; RPE; autophagy; heterophagy; inflammasome; lysosome; oxidative stress; phagocytosis; proteasome