中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (4): 385-393.doi: 10.4103/1673-5374.128240

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

抑制胶质细胞活化调控视网膜突触可塑性

  

  • 收稿日期:2014-01-04 出版日期:2014-02-25 发布日期:2014-02-25

Regulatory effects of inhibiting the activation of glial cells on retinal synaptic plasticity

Lihong Zhou, Hui Wang, Jia Luo, Kun Xiong, Leping Zeng, Dan Chen, Jufang Huang   

  1. Department of Human Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, Hunan Province, China
  • Received:2014-01-04 Online:2014-02-25 Published:2014-02-25
  • Contact: Jufang Huang, Ph.D., Department of Human Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, Hunan Province, China, huangjufang@csu.edu.cn. Dan Chen, Ph.D., Department of Human Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, Hunan Province, China, chendan0101@csu.edu.cn.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81070729; the Natural Science Foundation of Hunan Province in China, No. 10JJ4023; and the Hunan Provincial Innovation Foundation for Postgraduate in China, No. CX2011B047.

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摘要：

作者前期研究发现眼高压诱导的视网膜损伤以及其他的视网膜损伤可以诱导视网膜内突触发生可塑性的变化，但仍未阐明视网膜损伤后突触可塑性变化的机制，本次实验希望认识这一问题。给予大鼠眼前房穿刺注射生理盐水加压至14.63kPa (110mmHg)维持1h，建立急性高眼压模型，玻璃体腔注射胶质细胞代谢抑制剂氟代柠檬酸抑制神经胶质细胞的活化。Western blot和免疫荧光组织化学检测的结果显示，突触标记突触囊泡素的表达具有时空变化，高眼压后1d时在内网层表达，3d时扩大至外网层。高眼压后3d，视网膜中胶质纤维酸性蛋白表达明显增加，7d时达到峰值，这与急性高眼压后外网层中突触囊泡素表达峰值时间符合。以氟代柠檬酸治疗后，高眼压损伤导致的胶质纤维酸性蛋白表达增强明显受到抑制，且突触囊泡素在内网层分布明显减少，在外网层和外核层突触囊泡素增宽的分布消失。表明活化的视网膜神经胶质细胞可能通过影响突触囊泡素的表达和分布，进而参与调控急性高眼压损伤诱导的视网膜突触可塑性变化过程。

关键词: 神经再生, 神经可塑性, 胶质细胞, 高眼压, 视网膜, 氟代柠檬酸, 突触囊泡素, 胶质纤维酸性蛋白, 中国国家自然科学基金项目

Abstract:

Various retinal injuries induced by ocular hypertension have been shown to induce plastic changes in retinal synapses, but the potential regulatory mechanism of synaptic plasticity after retinal injury was still unclear. A rat model of acute ocular hypertension was established by injecting saline intravitreally for an hour, and elevating the intraocular pressure to 14.63 kPa (110 mmHg). Western blot assay and immunofluorescence results showed that synaptophysin expression had a distinct spatiotemporal change that increased in the inner plexiform layer within 1 day and spread across the outer plexiform layer after 3 days. Glial fibrillary acidic protein expression in retinae was greatly increased after 3 days, and reached a peak at 7 days, which was also consistent with the peak time of synaptophysin expression in the outer plexiform layer following the increased intraocular pressure. Fluorocitrate, a glial metabolic inhibitor, was intravitreally injected to inhibit glial cell activation following high intraocular pressure. This significantly inhibited the enhanced glial fibrillary acidic protein expression induced by high intraocular pressure injury. Synaptophysin expression also decreased in the inner plexiform layer within a day and the widened distribution in the outer plexiform layer had disappeared by 3 days. The results suggested that retinal glial cell activation might play an important role in the process of retinal synaptic plasticity induced by acute high intraocular pressure through affecting the expression and distribution of synaptic functional proteins, such as synaptophysin.

Key words: nerve regeneration, neuronal plasticity, retina, synapses, synaptophysin, glial cells, high intraocular pressure, fluorocitrate, glial fibrillary acidic protein, NSFC grant, neural regeneration