Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma

Glaucoma is an optic neuropathy with cupping of the optic disk, degeneratio n of retinal ganglion cells, and characteristic visual field loss. Because elevated intraocular pressure (IOP) is a major risk factor for progression of glaucoma, treatment has been based on lowering IOP, We previously demons trated inducible nitric-oxide synthase (NOS-2) in the optic nerve heads fro m human glaucomatous eyes and from rat eyes with chronic, moderately elevat ed IOP, Using this rat model of unilateral glaucoma, we treated a group of animals for 6 months with aminoguanidine, a relatively specific inhibitor o f NOS-2, and compared them with an untreated group. At 6 months, untreated animals had pallor and cupping of the optic disks in the eyes with elevated IOP, Eyes of aminoguanidine-treated animals with similar elevations of IOP appeared normal. We quantitated retinal ganglion cell loss by retrograde l abeling with Fluoro Gold. When compared with their contralateral control ey es with normal IOP, eyes with elevated IOP in the untreated group lost 36% of their retinal ganglion cells; the eyes with similarly elevated IOP in th e aminoguanidine-treated group lost less than 10% of their retinal ganglion cells, Pharmacological neuroprotection by inhibition of NOS-2 may prove us eful for the treatment of patients with glaucoma.