A prodrug of a selective inhibitor of inducible nitric oxide synthase is neuroprotective in the rat model of glaucoma

Purpose: To test the hypothesis that nitric oxide, synthesized by inducible nitric oxide synthase, causes degeneration of retinal ganglion cells in an animal model of glaucoma. Methods: Rats with unilateral chronic, moderately elevated intraocular pressure were treated orally with L-N-6-(1-iminoethyl)lysine 5-tetrazole amide, a prodrug of an inhibitor of inducible nitric oxide synthase. The loss of retinal ganglion cells 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 retinal ganglion cells. Treatment with L-N-6-( 1-iminoethyl)lysine 5-tetrazole amide for seven months completely prevented the loss of retinal ganglion cells in eyes with chronic, moderately elevated intraocular pressure. When treatment with L-N-6-(1-aminoethyl)lysine 5-tetrazole amide was delayed and started after three months of chronic, moderately elevated intraccular pressure, further loss of retinal ganglion cells was prevented. Conclusion: Pharmacological neuroprotection with a selective inhtibitor of inducible nitric oxide synthase may be useful for the treatment of glaucoma.