DOCOSAHEXAENOIC AND EICOSAPENTAENOIC ACID PROTECT PHOTORECEPTORS FROM OXIDATIVE STRESS BY ACTIVATING ANTIOXIDANT DEFENSE SYSTEMS

DANIELA L AGNOLAZZA; POLITI LUIS E; NORA P ROTSTEIN

Aci trezza

Taller; International School Lipidomics in the nervous system cells; 2010

Oxidative stress is involved in inducing the apoptotic death of photoreceptors (PhRs) in neurodegenerative diseases in the retina. Previous work from our laboratory has shown that docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, protects rat retina PhRs from oxidative stress-induced apoptosis due to paraquat (PQ) treatment. We here investigated whether eicosapentaenoic acid (EPA), a DHA precursor, might similarly protect PhRs from oxidative stress, whether DHA protection was effective with other oxidants such as hydrogen peroxide (H2O2) and whether this protection might involve the activation of antioxidant defense mechanisms. We first supplemented rat retina neuronal cultures with EPA, DHA, palmitic, oleic and arachidonic acids and treated them at day 3 with 48 M PQ. Only EPA (3 µM) and DHA (6,7 µM) protected PhRs from PQ-induced oxidative stress. When we evaluated the fatty acid composition of EPA-supplemented neurons, we found no increase in EPA levels but a significant increase in DHA content, suggesting that retina neurons had the ability to synthesize DHA from EPA in vitro. We then evaluated H2O2 effect on retina neurons. H2O2 induced PhR apoptosis and led to an increase in the production of reactive oxygen species (ROS), measured by a fluorimetrical method using DCFDA. DHA prevented PhR apoptosis and decreased ROS formation after H2O2 addition. These results suggest that EPA protects PhRs through its conversion to DHA, while other fatty acids have no protective effects. The decrease in ROS production suggests that DHA might activate cell antioxidants defense mechanisms to promote PhR survival.