Protective role of excitatory amino acid antagonists in experimental retinal ischemia.
BACKGROUND
Excitatory amino acids and their analogues (NMDA, kainate and AMPA) are implicated in the pathogenesis of ischemic brain injury. In order to fully understand their involvement in the pathogenesis of retinal ischemic injury, we studied the electrophysiological and histopathological effects of two excitatory amino acid antagonists, cis-PDA and MK 801, in an experimental retinal ischemia model.


METHODS
The two antagonists were injected intravitreously 15 min before ischemia was induced by elevatory intraocular pressure caused by external compression. Electrophysiological and histopathological evaluation was made 48 h after 45 min transient ischemia.


RESULTS
The excitatory amino acid antagonists cis-PDA and MK 801 can partially protect against retinal ischemic injury; whereas the mean post-ischemic b-wave amplitude corresponded to 41% of the pre-ischemic value in the control group, it was 64% (P = 0.003) and 59% (P = 0.005) following administration of cis-PDA and MK 801 respectively. Histopathological study corroborated these data, showing significant differences for morphometric parameters (P = 0.011 and P = 0.007 respectively).


CONCLUSIONS
These preliminary results suggest the possibility of limiting excito-toxicity, one of the lesion-forming mechanisms in ischemic retinal injury.
Weber
M
M
Department of Ophthalmology, Louis Pasteur University, Strasbourg, France.
Bonaventure
N
N
Sahel
J A
JA
D000818:Animals; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology / Q000627:therapeutic use; D004596:Electroretinography; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D007267:Injections; D007511:Ischemia / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D010875:Pipecolic Acids / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D012160:Retina / Q000473:pathology; D012171:Retinal Vessels; D014822:Vitreous Body
D018691:Excitatory Amino Acid Antagonists; D010875:Pipecolic Acids; C029262:2,3-piperidinedicarboxylic acid; D016291:Dizocilpine Maleate