Figure 2: Dysregulated heterophagy in aged RPE cells is associated with the accumulation of lipofuscin. Incomplete digestion of POS accelerates the accumulation of vitamine A metabolites (lipofuscin) within aged RPE cells lysosomes and the deposits of lipid-protein complexes (drusen) between Bruch’s membrane and RPE cells. These aggregates and deposits collaborate with microenvironmental and genetic factors to disturb normal functions of the RPE cells, leading to photoreceptor dysfunction and macular degeneration. Impaired lysosomal POS clearance increases lipofuscin trapped in lysosome that increases detrimental oxidative stress. Inefficient autophagic flux weakens lysosomal function, which increases exocytosis of damaged proteins and activates drusen formation-associated inflammasomes.