Mechanisms of protein aggregation in the retinal pigment epithelial cells.
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 degrade especially cellular proteins damaged by oxidative stress. This review examines 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.
Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, PO Box 1627, FIN-70211 Kuopio, Finland. kai.kaarniranta@uef.fi
Kai
K
Kaarniranta
Juha
J
Hyttinen
Tuomas
T
Ryhanen
Johanna
J
Viiri
Tuomas
T
Paimela
Elisa
E
Toropainen
Iiris
I
Sorri
Antero
A
Salminen
D000818:Animals; D004705:Endocytosis; D005089:Exocytosis; D005136:Eye Proteins / Q000378:metabolism*; D006801:Humans; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism*
D005136:Eye Proteins