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Abstract
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.