Synthesis of docosahexaenoic acid from eicosapentaenoic acid in retina neurons protects photoreceptors from oxidative stress

SIMON, MARIA VICTORIA; AGNOLAZZA, DANIELA L; OLGA LORENA GERMAN; GARELLI, ANDRES; POLITI, LUIS; AGBAGA, MARTIN-PAUL; ANDERSON, ROBERT E; ROTSTEIN, NORA

JOURNAL OF NEUROCHEMISTRY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2016 vol. 136 p. 931 - 946

0022-3042

Oxidative stress is involved in activating photoreceptor death in several retinal degenerations.Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, protectscultured retina photoreceptors from apoptosis induced by oxidative stress and promotesphotoreceptor differentiation. Here we investigated whether eicosapentaenoic acid (EPA), ametabolic precursor to DHA, had similar effects and whether retinal neurons could metabolizeEPA to DHA. Adding EPA to rat retina neuronal cultures increased opsin expression andprotected photoreceptors from apoptosis induced by the oxidants paraquat (PQ) and hydrogenperoxide (H2O2). Palmitic, oleic, and arachidonic acids had no protective effect, showing thespecificity for DHA. We found that EPA supplementation significantly increased DHApercentage in retinal neurons, but not EPA percentage. Photoreceptors and glial cells expressed∆6 desaturase (FADS2), which introduces the last double bond in DHA biosynthetic pathway.Pre-treatment of neuronal cultures with CP-24879 hydrochloride, a ∆5/∆6 desaturase inhibitor,prevented EPA-induced increase in DHA percentage and completely blocked EPA protectionand its effect on photoreceptor differentiation. These results suggest that EPA promotedphotoreceptor differentiation and rescued photoreceptors from oxidative stress-inducedapoptosis through its elongation and desaturation to DHA. Our data show, for the first time, thatisolated retinal neurons can synthesize DHA in culture.