Huang Shouyue, Huang Ping, Liu Xiaohong, Lin Zhongjing, Wang Jing, Xu Shuo, Guo Lei, Leung Christopher Kai-Shun, Zhong Yisheng
Department of Ophthalmology, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, 197 Ruijin Er Road, 200025 Shanghai, China.
Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, 197 Ruijin Er Road, 200025 Shanghai, China.
Neuroscience. 2017 Jan 26;341:27-41. doi: 10.1016/j.neuroscience.2016.11.019. Epub 2016 Nov 24.
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 (HS) 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 HS level together with the retinal protein expressions of related synthases, and further investigated the effect of exogenous HS 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 HS level was detected along with the retinal protein expressions of HS-related synthases cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) in the COH rats. Retinal HS level and RGC survival were evaluated again after NaHS (a HS donor) treatment in the COH rats. The results showed that the COH model succeeded in simulating glaucoma features, and retinal HS 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 HS 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 HS had protective effect on RGCs and might be involved in the pathological mechanism of glaucomatous neuropathy.
青光眼是一种不可逆的致盲性眼部神经退行性疾病,其特征是视网膜神经节细胞(RGCs)逐渐丧失。自从内源性硫化氢(HS)被报道参与中枢神经系统的神经退行性变以来,作者旨在建立一种模拟青光眼的慢性高眼压(COH)大鼠模型,并检测其中的HS水平以及相关合成酶的视网膜蛋白表达,进一步研究外源性补充HS对RGC存活的影响。通过向前房注射交联水凝胶诱导建立COH大鼠模型,并通过测量眼压(IOP)、计数RGCs和进行视网膜形态分析来评估模型的性能。检测COH大鼠内源性HS水平以及HS相关合成酶胱硫醚β合成酶(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COH大鼠接受NaHS(一种HS供体)治疗后,再次评估视网膜HS水平和RGC存活情况。结果表明,COH模型成功模拟了青光眼特征,并且在COH大鼠中,当CBS、CSE和3-MST的视网膜蛋白表达普遍下调时,视网膜HS水平显著降低。此外,在实验性青光眼中,NaHS治疗改善了视网膜HS水平的降低和RGCs的丧失,而眼压没有明显变化。我们的研究表明,前房内注射交联水凝胶在青光眼建模中有效,并且HS对RGCs具有保护作用,可能参与青光眼性神经病变的病理机制。