MECHANISM OF THE PATHOGENESIS OF GLUTAMATE NEUROTOXICITY IN RETINAL ISCHEMIA

Purpose: This study was carried out to examine the involvement of glut amate and nitric oxide neurotoxicity in ischemia/reperfusion-induced r etinal injury in vivo. Methods: We monitored glutamate release from in vivo cat retina during and after pressure-induced ischemia using a mi crodialysis technique. Morphometric studies were performed to study th e effects of MK-801 (dizocilpine), L-NAME (N-omega-nitro-L-arginine me thyl ester), and D-NAME (NO-nitro-D-arginine methyl ester) on the hist ological changes in the rat retina induced by ischemia or intravitreal injection of NMDA (N-methyl-D-aspartate; 200 nmol). Results: A large release of glutamate occurred during ischemia, followed by a marked re lease after reperfusion. Histological changes occurred selectively in the inner part of the retina after ischemia as well as intravitreal in jection of NMDA. Pretreatment with intravenous injection of MK-801 or L-NAME significantly inhibited the ischemic injury of the inner retina . Intravitreal injection of L-NAME inhibited NMDA-induced neurotoxicit y in the retina. Conclusion: These findings indicate that nitric oxide mediates neurotoxic actions of glutamate which are responsible for is chemic injury in the retina.