Photocytotoxicity of lipofuscin in human retinal pigment epithelial cells

Lipofuscin accumulates with age in a variety of highly metabolically active cells, including the retinal pigment epithelium (RPE) of the eye, where it s photoreactivity has the potential for cellular damage. The aim of this st udy was to assess the phototoxic potential of lipofuscin in the retina. RPE cell cultures were fed isolated lipofuscin granules and maintained in basa l medium for 7 d. Control cells lacking granules were cultured in an identi cal manner. Cultures were either maintained in the dark or exposed to visib le light (2.8 mWcm(2)) at 37 degreesC for up to 48 h. Cells were subsequent ly assessed for alterations in cell morphology, cell viability, lysosomal s tability, lipid peroxidation. and protein oxidation. Exposure of lipofuscin -fed cells to short wavelength visible light (390-550 nm) caused lipid pero xidation (increased levels of malondialdehyde and 4-hydroxy-nonenal), prote in oxidation (protein carbonyl formation), loss of lysosomal integrity, cyt oplasmic vacuolation, and membrane blebbing culminating in cell death. This effect was wavelength-dependent because light exposure at 550 to 800 nm ha d no adverse effect on lipofuscin-loaded cells. These results confirm the p hotoxicity of lipofuscin in a cellular system and implicate it in cell dysf unction such as occurs in ageing and retinal diseases. (C) 2001 Elsevier Sc ience Inc.