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Autophagy. 2013 Jul;9(7):973-84. doi: 10.4161/auto.24546. Epub 2013 Apr 9.

Autophagy and heterophagy dysregulation leads to retinal pigment epithelium dysfunction and development of age-related macular degeneration.

Author information

1
Department of Ophthalmology; Institute of Clinical Medicine; University of Eastern Finland; Kuopio, Finland; Department of Ophthalmology; Kuopio University Hospital; Kuopio, Finland.

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.

KEYWORDS:

AMD; RPE; autophagy; heterophagy; inflammasome; lysosome; oxidative stress; phagocytosis; proteasome

PMID:
23590900
PMCID:
PMC3722332
DOI:
10.4161/auto.24546
[Indexed for MEDLINE]
Free PMC Article

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