Lutein and zeaxanthin protect photoreceptors from apoptosis induced by oxidative stress. Relation with docosahexaenoic acid.

CHUCAIR A.J.; ROTSTEIN NP.; SANGIOVANNI J.P.; DURING A.; CHEW E.P.; POLITI L.E.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE

Association for Research in Vision and Ophthalmology

Lugar: Rockville, MD 20852-1606; Año: 2007 vol. 48 p. 5168 - 5177

0146-0404

Purpose: Oxidative stress has been proposed as a major pathogenic factor in age-related macular degeneration (AMD), the leading cause of vision loss among elderly people of western European ancestry. Lutein (LUT) and zeaxanthin (ZEA), major components in macular pigment, are among retina antioxidants. Though xanthophyll intake may reduce the likelihood of having advanced AMD, direct evidence of neuroprotection is lacking. We have shown that docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, delays apoptosis and promotes differentiation of photoreceptors. We have now investigated whether LUT, ZEA and b-carotene (BC), major dietary carotenoids protected photoreceptors from oxidative stress and whether this protection was synergistic with that of DHA. Methods: Pure rat retinal neurons in culture, supplemented with LUT, ZEA or BC, with or without DHA, were subjected to oxidative stress induced with paraquat and hydrogen peroxide. Apoptosis, preservation of mitochondrial membrane potential, cytochrome C translocation and opsin expression were evaluated. Results: Pre-treatment with DHA, LUT, ZEA and BC reduced oxidative stress-induced apoptosis in photoreceptors, preserved mitochondrial potential and prevented cytochrome C release from mitochondria. ZEA and LUT also enhanced photoreceptor differentiation. In control cultures, photoreceptors failed to grow their characteristic outer segments; addition of DHA, ZEA or LUT increased opsin expression and promoted the development of outer segment-like processes. Conclusions: These results show for the first time a direct neuroprotection of xanthophylls on photoreceptors, and suggest that ZEA and LUT along with DHA might be important environmental cues that concur to promote photoreceptor survival and differentiation.