Lipofuscin-formation in retinal pigment epithelial cells is reduced by antioxidants

The accumulation of lipofuscin by retinal pigment epithelium may be an impo rtant feature in the pathogenesis of age-related macular degeneration, sugg esting the possibility that this common cause of blindness might be prevent ed or delayed by antioxidants. In support of this idea, we now report signi ficantly reduced formation of lipofuscin when the antioxidant substances lu tein, zeaxanthin, lycopene (carotenoids), or alpha -tocopherol were added t o rabbit and bovine (calf) retinal pigment epithelial (RPE) cells exposed t o normobaric hyperoxia (40%) and photoreceptor outer segments. Rabbit and c alf RPE cells were grown for 2 weeks with addition of one of the test subst ances every 48 h. The cellular uptake of carotenoids and alpha -tocopherol was assayed by HPLC after 2 weeks. The lipofuscin-content was measured by s tatic fluorometry (rabbit cells) or by image analysis (calf cells). Both ra bbit and calf RPE showed similar results with significantly lower amounts o f lipofuscin in antioxidant-treated cells. The effect of carotenoids is esp ecially interesting, since the result is not dependent on their protective effect against photo-oxidative reactions. The chain-breaking abilities of t hese antioxidants in peroxidative reactions of lipid membranes and quenchin g of free radicals seem to be of importance for inhibition of lipofuscin fo rmation. (C) 2001 Elsevier Science Inc.