Effects of docosahexaenoic acid on retinal development: Cellular and molecular aspects

We have recently shown that docosahexaenoic acid (DHA) is necessary for sur vival 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 t o extensive degeneration of these cells by day 11. DHA protected photorecep tors. by delaying the onset of apoptosis; in addition, it advanced photorec eptor differentiation, promoting opsin expression and inducing apical diffe rentiation in these neurons. DHA was the only fatty acid having these effec ts. Mitochondrial damage accompanied photoreceptor apoptosis and was marked ly reduced upon DHA supplementation. This suggests that a possible mechanis m of DHA-mediated photoreceptor protection might be the preservation of mit ochondrial activity; a critical amount of DHA in mitochondrial phospholipid s might be required for proper functioning of these organelles, which in tu rn might be essential to avoid cell death. Muller cells in culture appeared to be involved in DHA processing: they took up DHA, incorporate it into gl ial phospholipids, and channeled it to photoreceptors in coculture. Both Mu ller cells, when cocultured with neuronal cells, and the glial-derived neur otrophic factor (GDNF) protected photoreceptors from cell death. These resu lts suggest that glial cells may play a central role in regulating photorec eptor 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 t hese cells.