Mechanism of the pathogenesis of glutamate neurotoxicity in retinal ischemia.
OBJECTIVE
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.


CONCLUSIONS
These findings indicate that nitric oxide mediates neurotoxic actions of glutamate which are responsible for ischemic injury in the retina.
Adachi
K
K
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Kashii
S
S
Masai
H
H
Ueda
M
M
Morizane
C
C
Kaneda
K
K
Kume
T
T
Akaike
A
A
Honda
Y
Y
D000818:Animals; D002415:Cats; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D007429:Intraocular Pressure / Q000502:physiology; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000503:physiopathology
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D019331:NG-Nitroarginine Methyl Ester