Retinyl palmitate and the blue-light-induced phototoxicity of human ocularlipofuscin

Lipofuscin accumulation in the retinal pigment epithelium is associated wit h the onset of age-related macular degeneration. Lipofuscin is phototoxic a nd affects cellular function through the photochemical generation of reacti ve oxygen intermediates. Mass spectral analysis of solvent extracts of huma n retinal lipofuscin granules reveals the presence of retinyl palmitate, th e substrate for the enzymatic regeneration of 11-cis-retinal. Retinyl palmi tate has an appreciable binding constant for phosphatidylcholine liposomes, and based on the glycophospholipids present in lipofuscin, retinal palmita te likely accumulates within the lipid content of the granule. Photochemica l oxidation of retinal palmitate generates anhydroretinol, an intracellular signaling retinoid in the signal transduction cascade from the plasma memb rane that causes apoptosis by generating reactive oxygen intermediates. The se data are used to propose a model for the phototoxicity of lipofuscin. (C ) 2001 Academic Press.