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经视网膜电刺激对退变视网膜内核层神经元的神经保护作用。

Neuroprotective effect of transretinal electrical stimulation on neurons in the inner nuclear layer of the degenerated retina.

作者信息

Schmid Heiko, Herrmann Thoralf, Kohler Konrad, Stett Alfred

机构信息

NMI Natural & Medical Sciences Institute at the University of Tuebingen, Markwiesenstr. 55, 72770 Reutlingen, Germany.

出版信息

Brain Res Bull. 2009 Apr 6;79(1):15-25. doi: 10.1016/j.brainresbull.2008.12.013. Epub 2009 Jan 15.

Abstract

Electrical stimulation has been shown to have neuroprotective effects on ganglion cells and photoreceptors in axotomized and dystrophic retinas from Royal College of Surgeons (RCS) rats. This study determined whether electrical stimulation also has a neuroprotective effect on cells in the inner nuclear layer (INL) of retinas. We cultivated retinas from adult RCS rats on microelectrode arrays and stimulated them continuously with 20 Hz for up to 5 days. Afterwards, we subjected them to quantitative immunohistochemical analysis. Using TUNEL assay we found that transretinal electrical stimulation (TRES) with charge densities within the range of 100-500 microC/cm2 reduced apoptosis of neurons in the INL of degenerated retinas from RCS -/- rats by 20% after 1 day of continuous stimulation. Antibody staining (OX-42, ED1) revealed a reduced activation of migroglial cells in RCS -/- and congenic control (RCS +/+) rat retinas by up to 50% after 1 day of stimulation. The effect of electrical stimulation on apoptosis and reduced activation of microglial cells was closely correlated with the strength and duration of the stimulation. The neuroprotective effect of TRES on neuronal cells in the INL of degenerated RCS rat retinas supports the idea that electrical stimulation may be a therapeutic option to delay the progression of retinal degeneration in patients suffering from retinitis pigmentosa.

摘要

电刺激已被证明对皇家外科医学院(RCS)大鼠的轴突切断和营养不良视网膜中的神经节细胞和光感受器具有神经保护作用。本研究确定电刺激是否对视网膜内核层(INL)中的细胞也具有神经保护作用。我们在微电极阵列上培养成年RCS大鼠的视网膜,并用20Hz连续刺激长达5天。之后,对它们进行定量免疫组织化学分析。使用TUNEL检测,我们发现电荷密度在100-500μC/cm²范围内的经视网膜电刺激(TRES)在连续刺激1天后,使RCS -/-大鼠退化视网膜INL中的神经元凋亡减少了20%。抗体染色(OX-42、ED1)显示,刺激1天后,RCS -/-和同基因对照(RCS +/+)大鼠视网膜中的小胶质细胞激活减少了多达50%。电刺激对凋亡和小胶质细胞激活减少的影响与刺激的强度和持续时间密切相关。TRES对退化的RCS大鼠视网膜INL中神经元细胞的神经保护作用支持了电刺激可能是延缓色素性视网膜炎患者视网膜退化进展的一种治疗选择的观点。

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