Protective effects of Xanthophylls and Docosahexaenoic acid on retinal photoreceptors

CHUCAIR A., SANGIOVANNI J.P; DURING A.; ROTSTEIN N ., POLITI L

Buenos Aires

Congreso; XVII International Congress of Eye Research (ICER); 2006

International Congress of Eye Research

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly population in the Western countries. Oxidative stress has been proposed as the main risk factor involved in the development of this pathology that affects the retina, particularly in the cone-rich zone called the macula. Death of photoreceptors takes place because of their intense exposure to damaging stimuli (e.g. sunlight and high oxygen tension), with the consequent visual loss. Lutein (LUT) and zeaxanthin (ZEA), the major xanthophills found in the macula, have been proposed to be part of the molecular protection system against photo-oxidative damage by diminishing the levels of reactive oxygen species. We have previously shown that docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, delays apoptosis, regulates cell cycle progression, and promotes differentiation of photoreceptors. Multiple epidemiological studies report a protective relationship of xanthophyll intake with advanced AMD; however, direct evidence of the protective effects and their molecular basis are lacking. We here investigated whether xanthophills had a protective effect on photoreceptors and whether this protection was synergistic with that of DHA. Pure rat retinal neurons in culture, grown in a chemically defined medium, were supplemented with LUT, ZEA and beta-carotene (B-C) at day 0, with or without DHA at day 1, and were treated at day 3 with the oxidant paraquat (PQ). Cultures lacking xanthophills or DHA were used as controls. Opsin expression, mitochondrial functionality and apoptosis were then evaluated. After PQ treatment in cultures lacking xanthophills or DHA, more than 50% of the photoreceptors showed fragmented or pyknotic nuclei and less than 30% of these neurons preserved their mitochondrial functionality. Supplementation of the cultures with LUT, ZEA and DHA reduced PQ-induced apoptosis and preserved mitochondrial functionality. On the contrary, B-C did not show a significant protective effect. In addition, ZEA, LUT and DHA enhanced differentiation in photoreceptors. 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 conspicuous, outer segment-like processes in photoreceptors. These results show for the first time a direct neuroprotective effect of LUT and ZEA from oxidative damage on photoreceptors. As a whole, these effects suggest that ZEA and LUT along with DHA might be important environmental cues that concur to activate photoreceptor survival and differentiation.