S E G Nilsson¹, S Sundelin¹, U Wihlmark¹, K Roberg², U Brunk²
¹Linköping University, Department of Ophthalmology, Linköping, Sweden; ²Linköping University, Department of Pathology II, Linköping , Sweden
Purpose: To examine whether oxidative reactions are involved in lipofuscin (LF) formation in retinal pigment epithelial (RPE) cells, whether certain antioxidants can reduce LF formation, and whether LF-loaded RPE cells are more sensitive to blue light irradiation than unloaded control cells.
Material and methods: This report reviews our experimental work on cultured RPE cells, fed photoreceptor outer segments (POS) and cultured in different oxygen concentrations or exposed to antioxidants or to blue light. The cell content of LF and labelled POS, respectively, was estimated by measuring specific fluorescence.
Results: We showed that significantly more 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, which seems to be in agreement with the positive results of the recent ARED study of antioxidants in patients with soft drusen maculopathy. 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. Accumulation of LF reduced the phagocytic capacity of RPE cells significantly. 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.
Conclusions: LF formation in cultured RPE cells was promoted by oxidative reactions and reduced by antioxidants. LF accumulation reduced the phagocytic capacity of RPE cells, and exposure of LF-loaded RPE cells to short wavelength light damaged or killed these cells.
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