Huang Wanjing, Gao Fengjuan, Hu Fangyuan, Huang Jiancheng, Wang Min, Xu Ping, Zhang Rong, Chen Junyi, Sun Xinghuai, Zhang Shenghai, Wu Jihong
Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, China.
State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
Front Neurosci. 2018 Jul 20;12:489. doi: 10.3389/fnins.2018.00489. eCollection 2018.
Asiatic acid (AA), a pentacyclic triterpene derived from the tropical medicinal plant , has been widely used as an antioxidant and anti-inflammatory agent. Evidence regarding the neuroprotective properties of AA is emerging. However, the protective effects of AA and its mechanism in glaucoma are poorly understood. In the current study, we investigate the neuroprotective effect and mechanism of AA on retinal ganglion cells (RGCs) in a rat model of glaucoma. Elevated intraocular pressure (IOP) was induced in adult rats by injecting microspheres into the anterior chamber. AA was intravitreally injected into glaucomatous rats. RGC densities were analyzed by evaluating surviving RGC number of the retinal flatmounts and retinal sections, and the apoptotic cell number were evaluated by analyzing retinal sections. RGC function was assessed by measuring the photopic negative response (PhNR). Retinal Bcl-2, Bax, and cleaved caspase-3 expression were determined using a Simple Western System, real-time PCR and immunofluorescence staining. AA reduced the loss of RGCs and decreased the apoptotic RGC number. AA exerted neuroprotective effects and ameliorated retinal dysfunction in impaired RGCs in a rat model of glaucoma. AA protected RGCs by upregulating the expression of the antiapoptotic protein Bcl-2 and downregulating the expression of the pro-apoptotic proteins Bax and caspase-3. This study has provided important evidence indicating that AA may be a potential therapeutic agent for glaucoma.
积雪草苷（AA）是一种从热带药用植物中提取的五环三萜，已被广泛用作抗氧化剂和抗炎剂。关于AA神经保护特性的证据正在不断涌现。然而，AA在青光眼方面的保护作用及其机制尚不清楚。在本研究中，我们在青光眼大鼠模型中研究了AA对视网膜神经节细胞（RGCs）的神经保护作用及其机制。通过向前房注射微球诱导成年大鼠眼压升高。将AA玻璃体内注射到青光眼大鼠体内。通过评估视网膜平铺片和视网膜切片中存活的RGC数量来分析RGC密度，并通过分析视网膜切片来评估凋亡细胞数量。通过测量明视负反应（PhNR）来评估RGC功能。使用Simple Western系统、实时PCR和免疫荧光染色来测定视网膜Bcl-2、Bax和裂解的caspase-3表达。AA减少了RGCs的损失并减少了凋亡RGC的数量。在青光眼大鼠模型中，AA对受损的RGCs发挥了神经保护作用并改善了视网膜功能障碍。AA通过上调抗凋亡蛋白Bcl-2的表达和下调促凋亡蛋白Bax和caspase-3的表达来保护RGCs。本研究提供了重要证据，表明AA可能是一种潜在的青光眼治疗药物。
