PROTECTIVE ROLES OF DOCOSAHEXAENOIC ACID AND XANTHOPHYLLS ON PHOTORECEPTORS

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

Fort Myers, Florida, EEUU

Conferencia; ARVO. Summer eye research conference (SERC); 2006

PROTECTIVE ROLES OF DOCOSAHEXAENOIC ACID AND XANTHOPHYLLS ON PHOTORECEPTORS Politi L.(1), Chucair A.(1), SanGiovanni J.P(2), German O.L.(1), During A. (3), and Rotstein N.(1) (1) Instituto de Investigaciones Bioquímicas, UNS-CONICET, Bahía Blanca, Argentina;(2) Clinical Trials Branch, NEI-NIH, Bethesda, MD; (3) USDA-ARS, Beltsville, MD. Purpose: Photoreceptor death is the main cause of several retinal degenerative diseases, such as macular degeneration. Though several photoreceptor survival factors have been identified, the cues for avoiding photoreceptor death are still missing. We have 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 this protective effect is lacking. We investigated the signaling pathways involved in DHA protection and whether the diet-based xanthophylls lutein (LUT) and zeaxanthin (ZEA) could also act to protect photoreceptors from oxidative stress. Methods: We used purified neuronal rat retina cultures grown in a chemically defined medium. Neurons were treated with inhibitors of enzymes of the ERK/MAPK or the PI3K pathway. Cultures without or with DHA, ZEA, or LUT were treated with the oxidant paraquat (PQ). Opsin expression, mitochondrial function and apoptosis were then evaluated. Results: Inhibition of the ERK/MAPK pathway blocked DHA-stimulated survival and differentiation of photoreceptors. Pre-treatment of the cultures with DHA, LUT and ZEA reduced PQ-induced apoptosis and preserved mitochondrial function. Both xanthophylls and DHA promoted further differentiation in photoreceptors. In control cultures, photoreceptors failed to grow their characteristic outer segments. Addition of DHA or carotenoids increased opsin expression and promoted the development of conspicuous outer segment-like processes in photoreceptors. Conclusions: These results suggest that DHA activated the ERK/MAPK pathway to promote photoreceptor survival, sharing the same signaling cascades with other trophic factors. They also show for the first time a direct neuroprotection of xanthophylls on photoreceptors, and suggest that ZEA and LUT along with DHA are important environmental cues that concur to activate photoreceptor survival and differentiation.