Melatonin: a novel neuroprotectant for the treatment of glaucoma
Melatonin: a novel neuroprotectant for the treatment of glaucoma
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DOI：
10.1111/j.1600-079x.2010.00762.x
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发表时间：
2010-05-01
影响因子：
10.3
通讯作者：
Rosenstein, Ruth E.
中科院分区：
文献类型：
--
作者：
Belforte, Nicolas A.;Moreno, Maria C.;Rosenstein, Ruth E.
青光眼是导致失明的主要原因。虽然高眼压是最重要的危险因素，但伴随的几个因素，如谷氨酸升高和γ-氨基丁酸(GABA)水平降低，NO代谢紊乱，以及氧化损伤都可能导致神经退行性变。本报告旨在分析褪黑素对大鼠视网膜谷氨酸清除、GABA浓度、NO合成和视网膜氧化还原状态的影响，以及对透明质酸(HA)诱导的慢性高眼压所致的功能和组织学改变的影响。在正常视网膜中，褪黑素增加谷氨酸摄取、谷氨酰胺合成酶活性、γ-氨基丁酸周转率、谷氨酸脱羧酶活性、超氧化物歧化酶活性和降低谷胱甘肽水平，而降低一氧化氮合酶活性、L-精氨酸摄取和脂质过氧化。为了评估褪黑素对青光眼神经病的疗效，每周在眼前房注射透明质酸。在第一次注射前24小时或每周注射六次HA后，皮下植入一粒褪黑素。褪黑素不影响眼压(IOP)，可预防和逆转高眼压对视网膜功能的影响(通过视网膜电图仪进行评估)，并降低视网膜神经节细胞对高眼压有害影响的脆弱性。这些结果表明褪黑素可能是治疗青光眼的一种有希望的资源。
Glaucoma is a leading cause of blindness. Although ocular hypertension is the most important risk factor, several concomitant factors such as elevation of glutamate and decrease in gamma-aminobutyric acid (GABA) levels, disorganized NO metabolism, and oxidative damage could significantly contribute to the neurodegeneration. The aim of this report was to analyze the effect of melatonin on retinal glutamate clearance, GABA concentrations, NO synthesis, and retinal redox status, as well as on functional and histological alterations provoked by chronic ocular hypertension induced by intracameral injections of hyaluronic acid (HA) in the rat eye. In normal retinas, melatonin increased glutamate uptake, glutamine synthase activity, GABA turnover rate, glutamic acid decarboxylase activity, superoxide dismutase activity, and reduced glutathione (GSH) levels, whereas it decreased NOS activity, L-arginine uptake, and lipid peroxidation. To assess the effect of melatonin on glaucomatous neuropathy, weekly injections of HA were performed in the eye anterior chamber. A pellet of melatonin was implanted subcutaneously 24 hr before the first injection or after six weekly injections of HA. Melatonin, which did not affect intraocular pressure (IOP), prevented and reversed the effect of ocular hypertension on retinal function (assessed by electroretinography) and diminished the vulnerability of retinal ganglion cells to the deleterious effects of ocular hypertension. These results indicate that melatonin could be a promissory resource in the management of glaucoma.