Nω-Nitro-L-arginine methyl ester protects retinal neurons against N-methyl-D-aspartate-induced neurotoxicity in vivo

Abstract We investigated whether the inhibition of nitric oxide (NO) synthesis with N ω -nitro- l -arginine methyl ester ( l -NAME), a competitive inhibitor of NO synthase, affects N -methyl- d -aspartate (NMDA)-induced neurotoxicity in the rat retina in vivo. A single intravitreal injection of NMDA damaged the ganglion cell layer and the inner plexiform layer without affecting the other retinal layers 7 days after injection. Intravitreal injection of (5 R ,10 S )-(+)-5-methyl-10,11-dihydro-5 H -dibenzo[ a , d ]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) with NMDA significantly reduced NMDA-induced degeneration of the retina. NMDA-induced degeneration was also prevented by intravitreal injection of l -NAME but not of d -NAME. The protective effect of l -NAME was antagonized by l -arginine. These results suggest that NO plays an important role in NMDA-induced excitotoxic degeneration in the retina.