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S-I Kawai, S Das, S Vora, EN Gachie, PT Manning, JR Connors, AH Neufeld; A Prodrug of a Selective Inhibitor of Inducible Nitric Oxide Synthase Is Neuroprotective In The Rat Model of Glaucoma . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2192.
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Purpose:We have previously presented data that indicates that nitric oxide neurotoxicity causes the optic neuropathy associated with glaucoma. To test the hypothesis that pharmacological inhibition of inducible nitric oxide synthase (NOS-2) will be useful for the treatment of the optic neuropathy associated with glaucoma, we have tested a selective and potent inhibitor of NOS-2 in a rat model of glaucoma. Methods:Unilateral, chronic, moderately elevated intraocular pressure was created in rats by cautery of three episcleral vessels. Rats were treated orally with L-N6-(1-iminoethyl)lysine 5-tetrazole amide (SC-51), a prodrug of an inhibitor of inducible nitric oxide synthase. SC-51 was started at the time of episcleral vessel cautery or three months after episcleral vessel cautery. Retinal ganglion cells (RGCs) were retrogradely labeled with Fluoro-Gold. The loss of RGCs was quantitated as an indicator of glaucomatous damage. Results:At the end of seven months, rat eyes with chronic, moderately elevated intraocular pressure lost approximately 20,000 RGCs. Treatment with SC-51 over a seven months period completely prevented the loss of RGCs in eyes with chronic, moderately elevated intraocular pressure. When treatment with SC-51 was delayed and started after three months of chronic, moderately elevated intraocular pressure, further loss of RGCs was prevented. Treatment with SC-51 did not affect intraocular pressure, body weight or water drinking. Conclusion:Pharmacological neuroprotection with a selective and potent inhibitor of inducible nitric oxide synthase may be useful for the treatment of glaucoma.
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