Docosahexaenoic acid promotes differentiation of developing photoreceptors in culture.

PURPOSE The purpose of this work was to study the effects of diverse fatty acids on the composition, metabolism, differentiation, and characteristics of opsin expression in retina photoreceptors. METHODS Cultures of rat retinal neurons were incubated with or without 22:6 n-3, 22:5 n-3, 20:4 n-6, 18:1 n-9, and 16:0, labeled and unlabeled. RESULTS In photoreceptor cells incubated with 22:6 n-3 and 22:5 n-3, the proportions of these fatty acids in phospholipids increased four- to sixfold. The remaining fatty acids did not change lipid acyl chain composition. The labeled fatty acids were all actively esterified in neuronal lipids, particularly in phosphatidylcholine. Addition of unlabeled 22:6 n-3 did not affect the distribution among lipids of the other fatty acids but displaced [3H]20:4 n-6 from phosphatidylcholine and phosphatidylethanolamine. These results suggest that retinal neurons have specific mechanisms for processing fatty acids of different lengths and degrees of unsaturation and that 22:6 n-3 incorporation takes priority. Of all fatty acids, 22:6 n-3 was the most effective in promoting photoreceptor differentiation. In 22:6-sufficient photoreceptors, new apical processes formed, the expression of opsin augmented, and its localization improved, concentrating in the apical processes of the cells. CONCLUSIONS The advancement in differentiation selectively elicited by 22:6 correlates with the fact that 22:6 n-3, but none of the other fatty acids, delays significantly the onset of apoptosis in photoreceptors in culture. The synthesis of 22:6-containing phospholipid molecules could be required for the proper localization of opsin. This could contribute to furthering the differentiation of photoreceptors, preventing their apoptosis, and extending their survival.