Wang Jia-Wei, Liu Yao-Ming, Zhao Xiao-Fei, Zhang Han
Eye Center of Shandong University, the Second Hospital of Shandong University, Shandong University, Jinan 250033, Shandong Province, China.
Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou 510060, Guangdong Province, China.
Int J Ophthalmol. 2017 Oct 18;10(10):1483-1489. doi: 10.18240/ijo.2017.10.01. eCollection 2017.
To investigate the neuroprotective effect of gastrodin on retinal ganglion cells (RGCs) in an acute ocular hypertension (AOH) rat model and to identify its possible mechanism.
AOH rat model was performed in a randomly selected eye by anterior chamber perfusion and either received an intraperitoneal injection with various concentrations of gastrodin or normal saline. After 2wk, the rats were sacrificed. FluoroGold was used to label survival RGCs. Immunostaining with anti-Iba1 in the retinal flat mounts to calculate the microglia density in the ganglion cell layer (GCL). Changes in microglial cytokines, tumour necrosis factor-alpha (TNF-α) and inducible NO synthase (iNOS) were examined with Western blot and reverse transcription-quantitative polymerase chain reaction. Expression levels of total and phosphorylated p38 mitogen activated protein kinase (MAPK) were determined by Western blot.
Results showed that AOH induced significant loss of RGCs and severe microglia activation in the GCL. Besides, AOH increased the phosphorylation of p38 MAPK and promoted the release of microglial cytokines in the retinas. Intraperitoneal injection with dose-dependent gastrodin significantly reduced the loss of RGCs and inhibited retinal microglia activation, accompanied with the decreased expression levels of microglial cytokines and p38 MAPK phosphorylation.
Gastrodin exerts a neuroprotective effect on RGCs in an acute glaucoma animal model inhibiting microglia activation and microglial-mediated neuroinflammation. The finding demonstrates the potential application of gastrodin in the neuroprotective therapy of acute glaucoma and other retinal neurodegenerative diseases characterized by microglia activation and RGCs death.
研究天麻素对急性高眼压（AOH）大鼠模型视网膜神经节细胞（RGCs）的神经保护作用，并确定其可能机制。
通过前房灌注在随机选择的一只眼睛中建立AOH大鼠模型，然后腹腔注射不同浓度的天麻素或生理盐水。2周后处死大鼠。用荧光金标记存活的RGCs。在视网膜铺片中用抗Iba1进行免疫染色，以计算神经节细胞层（GCL）中小胶质细胞的密度。用蛋白质免疫印迹法和逆转录-定量聚合酶链反应检测小胶质细胞细胞因子、肿瘤坏死因子-α（TNF-α）和诱导型一氧化氮合酶（iNOS）的变化。通过蛋白质免疫印迹法测定总p38丝裂原活化蛋白激酶（MAPK）和磷酸化p38丝裂原活化蛋白激酶的表达水平。
结果显示，AOH导致RGCs显著丢失，GCL中小胶质细胞严重活化。此外，AOH增加了视网膜中p38 MAPK的磷酸化，并促进了小胶质细胞细胞因子的释放。腹腔注射剂量依赖性的天麻素可显著减少RGCs的丢失，并抑制视网膜小胶质细胞的活化，同时伴随着小胶质细胞细胞因子表达水平的降低和p38 MAPK磷酸化的减少。
天麻素在急性青光眼动物模型中对RGCs具有神经保护作用，可抑制小胶质细胞活化和小胶质细胞介导的神经炎症。这一发现表明天麻素在急性青光眼和其他以小胶质细胞活化和RGCs死亡为特征的视网膜神经退行性疾病的神经保护治疗中具有潜在应用价值。
