Mechanism of the pathogenesis of glutamate neurotoxicity in retinal ischemia

Graefes Arch Clin Exp Ophthalmol. 1998 Oct;236(10):766-74. doi: 10.1007/s004170050156.


Purpose: This study was carried out to examine the involvement of glutamate and nitric oxide neurotoxicity in ischemia/reperfusion-induced retinal injury in vivo.

Methods: 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).

Results: 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.

Conclusion: These findings indicate that nitric oxide mediates neurotoxic actions of glutamate which are responsible for ischemic injury in the retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cats
  • Dizocilpine Maleate / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / metabolism
  • Glutamic Acid / physiology*
  • Intraocular Pressure / physiology
  • Ischemia / pathology
  • Ischemia / physiopathology*
  • Male
  • N-Methylaspartate / pharmacology
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Neuroprotective Agents / pharmacology
  • Neurotoxins / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow / physiology
  • Retina / drug effects
  • Retina / metabolism
  • Retina / pathology
  • Retinal Vessels* / physiopathology


  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Neuroprotective Agents
  • Neurotoxins
  • Glutamic Acid
  • N-Methylaspartate
  • Dizocilpine Maleate
  • NG-Nitroarginine Methyl Ester