Suppression of N-Methyl-N-Nitrosourea-Induced Photoreceptor Apoptosis in Rats by Docosahexaenoic Acid

Abstract

We evaluated the effects of dietary intake of docosahexaenoic acid (DHA) on photoreceptor cell apoptosis caused by N-methyl-N-nitrosourea (MNU). Five-week-old female Sprague-Dawley rats were fed basal diet (AIN-76A) or DHA diet (modified AIN-76A containing 9.5% DHA) for 2 weeks, and then received a single intraperitoneal injection of 60 mg/kg body weight MNU at 50 days of age. Then, rats continued to receive the same diet or were switched to the opposite diet: group 1, basal diet before and after MNU injection; group 2, DHA diet before MNU injection and basal diet after MNU injection; group 3, basal diet before MNU injection and DHA diet after MNU injection; group 4, DHA diet before and after MNU injection (10 rats in each group). Rats were starved for 24 h, then sacrificed 3 or 7 days after MNU. Morphologically, at 3 days after MNU injection, photoreceptor cell apoptosis was advanced in group 1 compared with group 4. At this time point, as evaluated by retinal damage ratio [(length of retina less than 4 photoreceptor cells thick/whole retinal length) ×100], retinal damage was highest in group 1 (82.4 ± 5.1%), followed by group 2 (41.1 ± 7.3%), group 3 (24.7 ± 11.5%), and group 4 (6.6 ± 6.6%); severity tended to be inversely correlated with serum DHA composition. At 7 days after MNU injection, active signs of photoreceptor cell apoptosis ended in all MNU-treated groups, and retinal damage ratio was high in group 1 (88.4 ± 2.8%), whereas it remained low in groups 2, 3 and 4 (38.4 ± 15.2, 45.7 ± 9.8 and 46.9 ± 11.2%, respectively). High DHA composition during induction/signaling phase and/or effector phase of photoreceptor cell apoptosis can delay the onset of apoptosis and counteract progression of MNU retinotoxicity in rat retina. DHA may play a role in the suppression of MNU-induced photoreceptor cell apoptosis in rat retina.