Figure 3.

Protein aggregation in aged RPE cells is involved in AMD pathology. RPE cells are constantly exposed to oxidative stress. In daily visual cycle photoreceptor outer segments are phagocytosed by the RPE; this process is referred to as heterophagy. The cellular elements are degraded in the lysosomes. In aged RPE cells, lipofuscin accumulates in lysosomes as a result of a coincident decline of lysosomal enzyme activity and autophagy flux. Lipofuscin is an autooxidant that increases damage induced by oxidative stress in mitochondrial and nuclear DNA. Disturbed clearance and accumulated toxic compounds in RPE trigger the inflammation and explain the AMD-associated biogenesis of extracellular drusen formation. Melatonin both inhibits oxidative damage and suppresses inflammation.