This report reviews our experimental work on cultured retinal pigment epithelial (RPE) cells, fed native or UV-irradiated photoreceptor outer segments (POS). We showed that significantly more lipofuscin (LF) was formed in cells cultured in 40% oxygen than in cells cultured in 8% oxygen, indicating an involvement of oxidative mechanisms in LF formation. The antioxidants alpha-tocopherol, lycopene, zeaxanthin and lutein significantly reduced LF formation. RPE cells high in melanin content exhibited significantly less formation of LF than cells low in or devoid of melanin, suggesting that melanin acts as an effective antioxidant. The phagocytic capacity of LF-loaded RPE cells was significantly reduced compared to that of unloaded control cells, indicating that LF-loaded RPE cells may be unable to serve the photoreceptors sufficiently regarding phagocytosis of shed outer segment tips. Blue light irradiation destabilized lysosomal membranes in LF-loaded RPE cells and significantly reduced the viability of such cells compared to unloaded, irradiated control cells. These results may be of significance in relation to the development of age-related macular degeneration (AMD).