Inducible nitric oxide synthase in retinal ischemia-reperfusion injury.
The purpose of this study was to determine whether inducible nitric oxide synthase (iNOS) was implicated in the pathogenesis of retinal ischemia-reperfusion injury. Semi-quantitative reverse transcription-polymerase chain reaction showed that the level of iNOS mRNA expression was markedly increased in rat retina following transient ischemia, with peak expression at 12 hr after reperfusion (15.7-fold increase over pre-ischemic levels). In situ hybridization showed that iNOS mRNA was expressed by resident retinal cells, most likely glial cells in the innermost retina, and also by the neutrophils that had infiltrated the retina. Intraperitoneal administration of NG-(1-iminoethyl)-L-ornithine (L-NIO), an inhibitor of iNOS, significantly increased the rate of b-wave recovery compared to that of control animals. The values (mean +/- S.E.M.) were 55.0 +/- 4.4% versus 40.1 +/- 5.1% (P < 0.05) at 1 day and 68.6 +/- 6.6% versus 45.8 +/- 3.5% (P < 0.05) at 3 days. This study shows that iNOS mRNA is highly expressed by non-neuronal cells of the inner retina during reperfusion following transient retinal ischemia. It also shows that L-NIO treatment provides some protection against ischemia-reperfusion injury. We suggest that nitric oxide produced by iNOS may mediate retinal ischemia-reperfusion injury.
Hangai
M
M
Department of Ophthalmology and Visual Science, Kyoto University Graduate School of Medicine, Japan.
Yoshimura
N
N
Hiroi
K
K
Mandai
M
M
Honda
Y
Y
D000818:Animals; D004596:Electroretinography; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009952:Ornithine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology* / Q000517:prevention & control; D012160:Retina / Q000201:enzymology*
D012333:RNA, Messenger; C065027:N(G)-iminoethylornithine; D009952:Ornithine; D019001:Nitric Oxide Synthase