Effects of docosahexaenoic acid on retinal development: cellular and molecular aspects.

We have recently shown that docosahexaenoic acid (DHA) is necessary for survival and differentiation of rat retinal photoreceptors during development in vitro. In cultures lacking DHA, retinal neurons developed normally for 4 d; then photoreceptors selectively started an apoptotic pathway leading to extensive degeneration of these cells by day 11. DHA protected photoreceptors by delaying the onset of apoptosis; in addition, it advanced photoreceptor differentiation, promoting opsin expression and inducing apical differentiation in these neurons. DHA was the only fatty acid having these effects. Mitochondrial damage accompanied photoreceptor apoptosis and was markedly reduced upon DHA supplementation. This suggests that a possible mechanism of DHA-mediated photoreceptor protection might be the preservation of mitochondrial activity; a critical amount of DHA in mitochondrial phospholipids might be required for proper functioning of these organelles, which in turn might be essential to avoid cell death. Müller cells in culture appeared to be involved in DHA processing: they took up DHA, incorporated it into glial phospholipids, and channeled it to photoreceptors in coculture. Both Müller cells, when cocultured with neuronal cells, and the glial-derived neurotrophic factor (GDNF) protected photoreceptors from cell death. These results suggest that glial cells may play a central role in regulating photoreceptor survival during development through the provision of trophic factors. The multiple effects of DHA on photoreceptors suggest that, in addition to its structural role, DHA might be one of the trophic factors required by these cells.