Interplay between reactive oxygen species and autophagy in the course of age-related macular degeneration

Abstract

Pathological biomolecules such as lipofuscin, methylglyoxal-modified proteins (the major precursors of advanced glycationend products), misfolding protein deposits and dysfunctional mitochondria are source of oxidative stress and act as strong autophagic stimulators in age-related macular degeneration. Disturbed autophagy accelerates progression of the disease, since it leads to retinal cells’ death and activates inflammation by the interplay with the NLRP3 inflammasome complex. Vascular dysfunction and hypoxia, as well as circulating autoantibodies against autophagy regulators (anti-S100A9, anti-ANXA5, and anti-HSPA8, A9 and B4) compromise an autophagy-mediated mechanism as well. Metformin, the autophagic stimulator, may act as a senostatic drug to inhibit the senescent phenotype in the age-related macular degeneration. PGC-1α , Sirt1 and AMPK represent new therapeutic targets for interventions in this disease.