Transcorneal electrical stimulation rescues axotomized retinal ganglion cells by activating endogenous retinal IGF-1 system
Transcorneal electrical stimulation rescues axotomized retinal ganglion cells by activating endogenous retinal IGF-1 system
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DOI：
10.1167/iovs.04-1339
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发表时间：
2005-06-01
影响因子：
4.4
通讯作者：
Fukuda, Y
中科院分区：
文献类型：
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作者：
Morimoto, T;Miyoshi, T;Fukuda, Y
目的.研究经角膜电刺激（transcorneal electrical stimulation，TES）对切断轴突的视网膜节细胞存活的影响，并探讨TES的神经保护作用机制。成年雄性Wistar大鼠视神经（ON）切断后接受TES。在ON横断后7天，测定存活的RGC的密度，以评价TES的神经保护作用。用RT-PCR、北方印迹和Western印迹法检测TES后视网膜中胰岛素样生长因子（IGF）-1 mRNA和蛋白的表达。IGF-1蛋白在视网膜中的定位通过荧光化学法检测。ON横断后TES增加了轴突切断的RGCs在体内的存活率，并且拯救的程度取决于电荷的强度。RT-PCR和北方和Western印迹分析显示TES后视网膜中的内在IGF-1逐渐上调。免疫组织化学分析显示，IGF-1免疫反应最初定位于Muller细胞的端足，然后扩散到视网膜内层。结论。TES可以通过增加Muller细胞产生IGF-1的水平来拯救轴突切断的RGC。这些发现提供了一种新的治疗方法，以防止或延缓视网膜神经元的变性，而无需管理外源性神经营养因子。
PURPOSE. To investigate the effect of transcorneal electrical stimulation (TES) on the survival of axotomized RGCs and the mechanism underlying the TES-induced neuroprotection in vivo.METHODS. Adult male Wistar rats received TES after optic nerve (ON) transection. Seven days after the ON transection, the density of the surviving RGCs was determined, to evaluate the neuroprotective effect of TES. The levels of the mRNA and protein of insulin-like growth factor (IGF)-1 in the retina after TES were determined by RT-PCR and Northern and Western blot analyses. The localization of IGF-1 protein in the retina was examined by immunohistochemistry.RESULTS. TES after ON transection increased the survival of axotomized RGCs in vivo, and the degree of rescue depended on the strength of the electric charge. RT-PCR and Northern and Western blot analyses revealed a gradual upregulation of intrinsic IGF-1 in the retina after TES. Immunohistochemical analysis showed that IGF-1 immunoreactivity was localized initially in the endfeet of Muller cells and then diffused into the inner retina.CONCLUSIONS. TES can rescue the axotomized RGCs by increasing the level of IGF-1 production by Muller cells. These findings provide a new therapeutic approach to prevent or delay the degeneration of retinal neurons without the administration of exogenous neurotrophic factors.