Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma
Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma
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DOI：
10.1073/pnas.96.17.9944
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发表时间：
1999-08-17
影响因子：
11.1
通讯作者：
Becker, B
中科院分区：
文献类型：
--
作者：
Neufeld, AH;Sawada, A;Becker, B
青光眼是一种视神经病变，具有视盘杯状、视网膜神经节细胞变性和特征性视野丧失。由于升高的眼内压（IOP）是青光眼进展的主要危险因素，因此治疗一直基于降低IOP。我们先前证明了在来自人青光眼眼和患有慢性、中度升高的IOP的大鼠眼的视神经头中的诱导型一氧化氮合酶（NOS-2）。使用这种单侧青光眼的大鼠模型，我们用氨基胍治疗一组动物6个月，NOS-2的相对特异性抑制剂，并与未治疗组进行比较。在6个月时，未给药动物的眼睛出现苍白和视盘凹陷，IOP升高。氨基胍给药动物的眼睛出现相似的IOP升高，表现正常。我们用荧光金逆行标记定量视网膜神经节细胞损失。当与其对侧正常IOP的对照眼相比时，未治疗组中IOP升高的眼睛失去了36%的视网膜神经节细胞;氨基胍治疗组中IOP类似升高的眼睛失去了不到10%的视网膜神经节细胞。通过抑制NOS-2的药理学神经保护可能被证明对青光眼患者的治疗有用。
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.