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硫化氢补充剂可维持大鼠青光眼模型中视网膜神经节细胞的线粒体功能。

Hydrogen sulfide supplement preserves mitochondrial function of retinal ganglion cell in a rat glaucoma model.

机构信息

Department of Ophthalmology, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, Shanghai, China.

Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, Shanghai, China.

出版信息

Cell Tissue Res. 2022 Aug;389(2):171-185. doi: 10.1007/s00441-022-03640-x. Epub 2022 May 20.

Abstract

Glaucoma is a neurodegenerative disease of visual system characterized by gradual loss of retinal ganglion cells (RGC). Since mitochondrial dysfunction of RGC is significantly involved in the pathological mechanisms of glaucoma, and hydrogen sulfide (HS) takes part in the pathogeny of glaucoma and shows promising potential in restoring mitochondrial function in other neurons, the authors aimed to investigate the impact of HS on mitochondrial function of RGC with a rat glaucoma model. An established chronic ocular hypertension (COH) rat model induced by injection of cross-linking hydrogel into anterior chamber was adopted, and a HS donor, sodium hydrosulfide (NaHS), was selected to treat rats through intraperitoneal injection. After a period of 4 weeks, RGCs were isolated from the subjected rats with an immunopanning method and went through evaluations of mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (MPTP) opening, intracellular Ca2 + level, reactive oxygen species (ROS) level, and cytosolic Cytochrome C distribution. The results showed that the mitochondrial function of RGC in experimental glaucoma was markedly improved by HS supplement, being presented as stabilization of MMP, alleviation of MPTP opening, improvement of intracellular Ca hemostasis, reduction of ROS accumulation, and inhibition of Cytochrome C release. Our study implicated that preservation of mitochondrial function by HS probably plays a key role in protecting RGC in the context of glaucomatous neuropathy, and it is worth further deepgoing research to benefit the development of glaucoma treatment.

摘要

青光眼是一种以视网膜神经节细胞(RGC)逐渐丧失为特征的神经退行性视觉系统疾病。由于 RGC 的线粒体功能障碍与青光眼的病理机制密切相关,而硫化氢(HS)参与了青光眼的发病机制,并在恢复其他神经元的线粒体功能方面显示出巨大的潜力,作者旨在研究 HS 对青光眼大鼠模型中 RGC 线粒体功能的影响。采用前房注射交联水凝胶建立慢性高眼压(COH)大鼠模型,选择 HS 供体硫氢化钠(NaHS)通过腹腔注射治疗大鼠。4 周后,采用免疫淘选法从受影响的大鼠中分离出 RGC,并对线粒体膜电位(MMP)、线粒体通透性转换孔(MPTP)开放、细胞内 Ca2+水平、活性氧(ROS)水平和细胞质细胞色素 C 分布进行评估。结果表明,HS 补充显著改善了实验性青光眼大鼠的 RGC 线粒体功能,表现为 MMP 稳定、MPTP 开放减轻、细胞内 Ca 稳态改善、ROS 积累减少和细胞色素 C 释放抑制。我们的研究表明,HS 通过维持线粒体功能可能在青光眼神经病变中对保护 RGC 起着关键作用,值得进一步深入研究,以有利于开发青光眼的治疗方法。

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