Transcorneal electrical stimulation promotes survival of retinal ganglion cells after optic nerve transection in rats accompanied by reduced microglial activation and TNF-alpha expression.
Transcorneal electrical stimulation promotes survival of retinal ganglion cells after optic nerve transection in rats accompanied by reduced microglial activation and TNF-alpha expression.
复制标题
经角膜电刺激可促进大鼠视神经横断后视网膜神经节细胞的存活，同时减少小胶质细胞活化和 TNF-α 表达。
DOI：
10.1016/j.brainres.2016.08.034
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发表时间：
2016
期刊：
影响因子：
2.9
通讯作者：
Fang Xiaoyun
中科院分区：
文献类型：
--
作者：
Yin Houmin;Yin Houfa;Zhang Wei;Miao Qi;Qin Zhenwei;Guo Shenchao;Fu Qiuli;Ma Jian;Wu Fang;Yin Jinfu;Yang Yabo;Fang Xiaoyun
小胶质细胞激活在各种视网膜和视神经疾病的病理过程中起着至关重要的作用。肿瘤坏死因子-α是一种促炎细胞因子，在视神经损伤后迅速上调并促进视网膜神经节细胞(RGC)死亡。然而，视神经损伤后肿瘤坏死因子-α的细胞来源尚不清楚。因此，我们旨在研究大鼠视神经切断(ONT)模型经角膜电刺激(TES)后视网膜小胶质细胞活化的变化。此外，我们评估了ONT后肿瘤坏死因子-α的表达，并评价了TES对肿瘤坏死因子-α产生的影响。将大鼠分为假手术对照组、ONT+Sham TES组和ONT+TES组。于ONT后第7天或第14天处死大鼠。于ONT前7天用荧光金逆行标记视网膜节细胞，TES组和相应对照组分别于0、4、0、4、7、10天刺激RGCs，0、4、7、10天刺激TES组RGCs。于ONT后7、14 d进行整体免疫组织化学染色、RGCs和小胶质细胞定量及免疫印迹分析。TES显著增加ONT后第7天和第14天的RGCs存活率，第7天伴有小胶质细胞减少，而第14天未见。肿瘤坏死因子-α与阿米巴样小胶质细胞共存，在ONT后第7天和第14天显著增加。在ONT后第7天和第14天，TES显著降低肿瘤坏死因子-α的产生。我们的研究表明，TES促进了ONT后RGC的存活，同时伴随着小胶质细胞活化和小胶质细胞来源的肿瘤坏死因子-α的产生减少。
Microglial activation plays a crucial role in the pathological processes of various retinal and optic nerve diseases. TNF-α is a pro-inflammatory cytokine that is rapidly upregulated and promotes retinal ganglion cells (RGCs) death after optic nerve injury. However, the cellular source of TNF-α after optic nerve injury remains unclear. Thus, we aimed to determine the changes of retinal microglial activation in a rat model of optic nerve transection (ONT) after transcorneal electrical stimulation (TES). Furthermore, we assessed TNF-α expression after ONT and evaluated the effects of TES on TNF-α production. Rats were divided into 2 control groups receiving a sham surgery procedure, 2 ONT+Sham TES groups, and 2 ONT+TES groups. The rats were sacrificed on day 7 or 14 after ONT. RGCs were retrogradely labelled by Fluorogold (FG) 7 days before ONT, one TES group and corresponding controls were stimulated on day 0, 4, and the second were stimulated on day 0, 4, 7, 10. Whole-mount immunohistofluorescence, quantification of RGCs and microglia, and western blot analysis were performed on day 7 and 14 after ONT. TES significantly increased RGCs survival on day 7 and 14 after ONT, which was accompanied by reduced microglia on day 7, but not 14. TNF-α was co-localized with ameboid microglia and significantly increased on day 7 and 14 after ONT. TES significantly reduced TNF-α production on day 7 and 14 after ONT. Our study demonstrated that TES promotes RGCs survival after ONT accompanied by reduced microglial activation and microglia-derived TNF-α production.