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S Garg, RN Sanchez, Q Chu, TT Lam; Neuroprotective Effect Of NS-398, A Cyclooxygenase 2 (COX-2) Inhibitor, On Retinal Ischemia-Reperfusion Injury In Rats . Invest. Ophthalmol. Vis. Sci. 2002;43(13):777.
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Purpose:: To evaluate the neuroprotective effect of NS-398, an inhibitor of COX-2, as measured by retinal ganglion cell (RGC) survival in rat ischemia-reperfusion injury. Methods:Ischemia-reperfusion injury to the retina of 55-60 day old male Lewis albino rats was induced by elevating the intra-ocular pressure (IOP) by cannulation of the anterior chamber with a 27-gauge needle attached to a saline column delivering a pressure of 110 mmHg. The ischemic insult was maintained for 60 minutes. Retinal ischemia was confirmed by whitening of the anterior segment of the eye and the blanching of the retina. The study was performed with 5 groups of animals (number of eyes): normal (n=8), vehicle (n=5), 1 (n=6), 3 (n=6), and 10 (n=4) µM NS-398. Vehicle or NS-398 was infused into the eyes during the ischemic period. The animals were allowed to recover for 7 days then euthanized. The eyes were enucleated. The retinas were removed and flat-mounted to allow for RGC counting. Additionally, a single group of animals was subjected to the experimental condition (time course) and the retinal samples were also collected and used for dot-blot and Western analysis of COX-2. Results:Compared to the vehicle treated group, all NS-398 treated retinas showed beneficial effects as measured by RGC counts (P< 0.007; Tukey’s test). However, there was no statistical difference between the three drug treated groups. As compared to normal, the drug treated group showed approximately 75% RGC survival. Dot-blot analysis demonstrated an initial decrease of COX-2 level at 2 and 4 hours, and an increase above normal at 18 hours. Conclusion:NS-398, a COX-2 inhibitor, is neuroprotective in ischemia-reperfusion injury. Our findings suggest that COX-2 may be involved in inner retinal degeneration after retinal ischemia-reperfusion injury.
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