Mechanism of the pathogenesis of glutamate neurotoxicity in retinal ischemia

• DOI: 10.1007/s004170050156
• Publication Date: 2002-08-25T04:36:27Z
• Authors: K. Adachi; S. Kashii; Hirokazu Masai; Mutsuaki Ueda; Chikako Morizane; Katsuyuki Kaneda; Toshiaki Kume; Akinori Akaike; Yoshihito Honda
• Keywords: Male; N-Methylaspartate; Neurotoxins; Glutamic Acid; Retinal Vessels; Retina; Rats; Rats, Sprague-Dawley; 03 medical and health sciences; NG-Nitroarginine Methyl Ester; Neuroprotective Agents; 0302 clinical medicine; Ischemia; Regional Blood Flow; Cats; Excitatory Amino Acid Agonists; Animals; Dizocilpine Maleate; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Intraocular Pressure

This study was carried out to examine the involvement of glutamate and nitric oxide neurotoxicity in ischemia/reperfusion-induced retinal injury in vivo.We monitored glutamate release from in vivo cat retina during and after pressure-induced ischemia using a microdialysis technique. Morphometric studies were performed to study the effects of MK-801 (dizocilpine), L-NAME (N omega-nitro-L-arginine methyl ester), and D-NAME (N omega-nitro-D-arginine methyl ester) on the histological changes in the rat retina induced by ischemia or intravitreal injection of NMDA (N-methyl-D-aspartate; 200 nmol).A large release of glutamate occurred during ischemia, followed by a marked release after reperfusion. Histological changes occurred selectively in the inner part of the retina after ischemia as well as intravitreal injection 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 neurotoxicity in the retina.These findings indicate that nitric oxide mediates neurotoxic actions of glutamate which are responsible for ischemic injury in the retina.