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Age‐related modifications in RPE cells
Author(s) -
MANNERMAA E
Publication year - 2010
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2010.2231.x
Subject(s) - lipofuscin , macular degeneration , drusen , pathogenesis , retinal , autophagy , microbiology and biotechnology , retinal pigment epithelium , oxidative stress , proteasome , lysosome , retina , extracellular , biology , chemistry , medicine , immunology , endocrinology , biochemistry , neuroscience , ophthalmology , apoptosis , enzyme
Age‐related macular degeneration (AMD) is a multi‐factorial polygenetic aging disease. It has been shown that RPE dysfunction predisposes neural retinal dysfunction and the development of choroidal neovascularization. The pathogenesis of age‐related macular degeneration (AMD) essentially involves chronic oxidative stress, increased accumulation of lipofuscin in retinal pigment epithelial (RPE) cells and extracellular drusen formation, as well as the presence of chronic inflammation. The capacity to prevent the accumulation of cellular cytotoxic protein aggregates is decreased in senescent cells which may evoke lipofuscin accumulation into lysosomes in postmitotic RPE cells. This presence of lipofuscin decreases lysosomal enzyme activity and impairs autophagic clearance of damaged proteins which should be removed from cells. Proteasomes are another crucial proteolytic machine which degrades especially cellular proteins damaged by oxidative stress. The cross‐talk between lysosomes, autophagy and proteasomes in RPE cell protein aggregation, their role as a possible therapeutic target and their involvement in the pathogenesis of AMD is discussed. In addition, age related changes in Bruch’s membrane and choroidal blood flow may take part in the pathogenesis of AMD. This will be also discussed.