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经角膜电刺激通过激活内源性视网膜胰岛素样生长因子-1系统挽救轴突切断的视网膜神经节细胞。

Transcorneal electrical stimulation rescues axotomized retinal ganglion cells by activating endogenous retinal IGF-1 system.

作者信息

Morimoto Takeshi, Miyoshi Tomomitsu, Matsuda Satoshi, Tano Yasuo, Fujikado Takashi, Fukuda Yutaka

机构信息

Department of Physiology and Biosignaling, Osaka University Medical School, Japan.

出版信息

Invest Ophthalmol Vis Sci. 2005 Jun;46(6):2147-55. doi: 10.1167/iovs.04-1339.

Abstract

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.

摘要

目的

研究经角膜电刺激(TES)对轴突切断的视网膜神经节细胞(RGCs)存活的影响以及体内TES诱导神经保护作用的潜在机制。

方法

成年雄性Wistar大鼠在视神经(ON)横断后接受TES。ON横断7天后,测定存活RGCs的密度,以评估TES的神经保护作用。通过逆转录聚合酶链反应(RT-PCR)、Northern印迹和Western印迹分析测定TES后视网膜中胰岛素样生长因子(IGF)-1的mRNA和蛋白质水平。通过免疫组织化学检查IGF-1蛋白在视网膜中的定位。

结果

ON横断后进行TES可增加体内轴突切断的RGCs的存活,挽救程度取决于电荷强度。RT-PCR、Northern印迹和Western印迹分析显示TES后视网膜中内源性IGF-1逐渐上调。免疫组织化学分析表明,IGF-1免疫反应性最初定位于Muller细胞的终足,然后扩散到视网膜内层。

结论

TES可通过增加Muller细胞产生的IGF-1水平来挽救轴突切断的RGCs。这些发现提供了一种新的治疗方法,无需给予外源性神经营养因子即可预防或延缓视网膜神经元的退化。

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