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Tale of lysosome in RPE cells and in the pathogenesis of AMD
Author(s) -
SINHA D
Publication year - 2014
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.1755-3768.2014.2273.x
Subject(s) - lipofuscin , autophagy , lysosome , phagocytosis , pathogenesis , retinal pigment epithelium , inflammation , microbiology and biotechnology , macular degeneration , biology , retinal degeneration , immune system , retinal , retina , immunology , medicine , neuroscience , genetics , biochemistry , apoptosis , ophthalmology , enzyme
In RPE cells, the lysosomal system is a crucial regulator of both phagocytosis and autophagy. We have recently shown in the Nuc1 rat (a spontaneous mutation in the Cryba1 gene encoding for betaA3/A1‐crystallin) and in mice lacking betaA3/A1‐crystallin specifically in the RPE, that impaired lysosomal clearance decreases both autophagy and phagocytosis. This leads to the accumulation of lipofuscin within RPE cells, subretinal lesions in the posterior pole, and deposits between the RPE and Bruch’s membrane. It is likely that disturbances in the homeostasis of RPE cells, due to accumulation of undegraded intracellular material in the mice lacking betaA3/A1‐crystallin, trigger a para‐inflammatory response in an attempt to restore normal RPE function. Severe or prolonged impairment of lysosomal‐mediated clearance may also convert para‐inflammation to chronic inflammation, leading to retinal degeneration. Several studies support the hypothesis that the immune system is involved in the pathogenesis of AMD, in concert with, or in addition to, other factors. We have generated a genetically engineered mouse model that exhibits a slowly progressing form of AMD‐like pathology associated with inefficient lysosomal clearance.