Retinal pigment epithelium pigment granules stimulate the photo-oxidation of unsaturated fatty acids

The cellular pigments of the retinal pigment epithelium (RPE) have been sho wn to catalyze free radical activity, especially when illuminated with visi ble or ultraviolet light. This activity is sufficient to cause photooxidati on of several major cellular components. The present investigation determin ed the relative ability of melanin, lipofuscin, and melanolipofuscin granul es isolated from human and bovine eyes to oxidize polyunsaturated fatty aci ds, specifically linoleic and docosahexaenoic acids. The dark reactivity as well as the light-stimulated reactions were determined. The production of hydroperoxide derivatives of the linoleic and docosahexaenoic acids were de termined by NADPH oxidation coupled to the activity of glutathione peroxida se, and also by production of thiobarbituric acid reactive substances. All RPE pigment granules stimulated fatty acid oxidation when irradiated with s hort wavelength (<550 nm) visible light, with the melanosomes exhibiting th e greatest light-induced activity. Only lipofuscin granules, however, cause d peroxidation of fatty acids in the dark. These findings provide additiona l support for the role of RPE pigments in "blue light toxicity" as well as indicating that accumulation of lipofuscin may contribute to increased phot ooxidation in the aging RPE. (C) 1999 Elsevier Science Inc.