Neufeld A H, Sawada A, Becker B
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9944-8. doi: 10.1073/pnas.96.17.9944.
Glaucoma is an optic neuropathy with cupping of the optic disk, degeneration 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 demonstrated inducible nitric-oxide synthase (NOS-2) in the optic nerve heads from human glaucomatous eyes and from rat eyes with chronic, moderately elevated IOP. Using this rat model of unilateral glaucoma, we treated a group of animals for 6 months with aminoguanidine, a relatively specific inhibitor of 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 labeling with Fluoro-Gold. When compared with their contralateral control eyes 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 the aminoguanidine-treated group lost less than 10% of their retinal ganglion cells. Pharmacological neuroprotection by inhibition of NOS-2 may prove useful for the treatment of patients with glaucoma.
青光眼是一种伴有视盘凹陷、视网膜神经节细胞变性及特征性视野缺损的视神经病变。由于眼内压（IOP）升高是青光眼进展的主要危险因素，因此治疗一直基于降低眼内压。我们先前在人类青光眼患者的视神经乳头以及慢性中度眼内压升高的大鼠眼中证实了诱导型一氧化氮合酶（NOS-2）的存在。利用这种单侧青光眼大鼠模型，我们用氨基胍（一种相对特异的NOS-2抑制剂）对一组动物进行了6个月的治疗，并将其与未治疗组进行比较。6个月时，未治疗动物眼内压升高侧的视盘出现苍白和凹陷。氨基胍治疗组中眼内压类似升高的动物的眼睛看起来正常。我们通过用荧光金逆行标记来定量视网膜神经节细胞的损失。与对侧眼内压正常的对照眼相比，未治疗组中眼内压升高的眼睛损失了36%的视网膜神经节细胞；氨基胍治疗组中眼内压类似升高的眼睛损失的视网膜神经节细胞不到10%。通过抑制NOS-2进行药理神经保护可能对青光眼患者的治疗有用。
