RELEVANT VARIATIONS AND NEUROPROTECIVE EFFECT OF HYDROGEN SULFIDE IN A RAT GLAUCOMA MODEL

RELEVANT VARIATIONS AND NEUROPROTECIVE EFFECT OF HYDROGEN SULFIDE IN A RAT GLAUCOMA MODEL
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硫化氢在大鼠青光眼模型中的相关变化及神经保护作用

DOI:
10.1016/j.neuroscience.2016.11.019
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发表时间:
2017-01-26
期刊:
影响因子:
3.3
通讯作者:
Zhong, Yisheng
Zhong, Yisheng
中科院分区:
医学3区
文献类型:
--
作者:
Huang, Shouyue;Huang, Ping;Zhong, Yisheng

文献摘要

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青光眼是一种不可逆且致盲的眼部神经退行性疾病,其特征是视网膜神经节细胞(RGC)逐渐丧失。由于内源性硫化氢(H2S)被报道与中枢神经系统的神经退行性疾病有关,因此作者旨在建立模拟青光眼的慢性高眼压(COH)大鼠模型,并在其中测试H2S水平以及相关合酶的视网膜蛋白表达,并进一步研究外源性H2S补充对RGC存活的影响。通过前房注射交联水凝胶诱导COH大鼠模型,并通过眼压(IOP)测量、RGC计数和视网膜形态分析评估模型的性能。检测COH大鼠中内源性H2S水平以及H2S相关合成酶胱硫醚β-合酶(CBS)、胱硫醚γ-裂解酶(CSE)和3-巯基丙酮酸硫转移酶(3-MST)的视网膜蛋白表达。在对 COH 大鼠进行 NaHS(H2S 供体)治疗后,再次评估视网膜 H2S 水平和 RGC 存活率。结果表明,COH模型成功模拟了青光眼特征,当COH大鼠视网膜CBS、CSE和3-MST蛋白表达普遍下调时,视网膜H2S水平显着下降。此外,实验性青光眼中NaHS治疗均改善了视网膜H2S水平的降低和RGC的损失,且眼压没有明显变化。我们的研究表明,前房注射交联水凝胶可以有效地模拟青光眼,并且H2S对RGC具有保护作用,并可能参与青光眼神经病变的病理机制。 (C) 2016 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Glaucoma is an irreversible and blinding neurodegenerative disease of the eye, and is characterized by progressive loss of retinal ganglion cells (RGCs). Since endogenous hydrogen sulfide (H2S) was reported to be involved in neurodegeneration in the central nervous system, the authors aimed to develop a chronic ocular hypertension (COH) rat model simulating glaucoma and therein test the H2S level together with the retinal protein expressions of related synthases, and further investigated the effect of exogenous H2S supplement on RGC survival. COH rat model was induced by cross-linking hydrogel injection into anterior chamber, and the performance of the model was assessed by intraocular pressure (IOP) measurement, RGC counting and retinal morphological analysis. Endogenous H2S level was detected along with the retinal protein expressions of H2S-related synthases cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) in the COH rats. Retinal H2S level and RGC survival were evaluated again after NaHS (a H2S donor) treatment in the COH rats. The results showed that the COH model succeeded in simulating glaucoma features, and retinal H2S level decreased significantly when the retinal protein expressions of CBS, CSE and 3-MST were downregulated generally in the COH rats. Furthermore, the decrease of retinal H2S level and loss of RGCs were both improved by NaHS treatment in experimental glaucoma, without obvious variation of IOP. Our study revealed that the intracameral injection of cross linking hydrogel worked efficiently in modeling glaucoma, and H2S had protective effect on RGCs and might be involved in the pathological mechanism of glaucomatous neuropathy. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.