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Molecular mechanism of subtype specific death of retinal ganglion cells induced by different stimuli.

不同刺激诱导视网膜神经节细胞亚型特异性死亡的分子机制。

基本信息

批准号：
18591909
负责人：
WAKABAYASHI Taketoshi
金额：
$ 2.5万
依托单位：
Kansai Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591909/
关键词：
retinal ganglion cells optic nerve transection BH3-only protein rat ferret Bim 緑内障モデル

项目摘要

It has been well known that there are several subtypes of retinal ganglion cells (RGCs) discriminated by their soma sizes, dendrite morphology and electrophysiological properties. After optic nerve transaction, smaller types of RGCs die predominantly. By contrast, larger types of RGCs die earlier in glaucoma than the smaller type. However, the molecular mechanisms of subtype specific RGC death are not known yet.In this project, we first tried to determine which type of BH3-only protein genes are induced by optic nerve transaction and glaucoma model by quantitative polymerase chain reaction (PCR). One day after the optic nerve transaction, only a subset of BH3-only protein messenger RNA (mRNA) were induced. Most of the BH3-only protein genes examined were not changed statistically by optic nerve transaction. By contrast, intra-vitreal injection of N-methyl-D-aspartic acid, a glaucoma model, induced different type of BH3-only protein gene.Next, Bim protein expression was investigated on the optic nerve transected rat and ferret retinas by immunohistochemistry. In ferret retina, morphological and physiological properties of RGCs and their correlations are well studied. In rat retina, anti-Bim antibody labeled RGCs after optic nerve transection. On the flatmount retina, we tried to determine which type of RGCs predominantly expressing Bim protein. Soma size distribution of Bim expressing cells was different from that of all the surviving RGCs. This is the first report that Bim was induced predominantly in subtypes of RGCs. In ferret retina, Bim expressing RGCs were also investigated on the flatmount retina. We also demonstrated that Bim was expressing selectively in subtypes of RGC. These results strongly suggested that Bim and other BH3-only proteins contribute to subtype specific RGC death on different death inducing stimuli.

视网膜神经节细胞（retinal ganglion cells，RGCs）根据其索马大小、树突形态和电生理特性可分为多种亚型。视神经切断后，较小类型的RGC主要死亡。相比之下，较大类型的RGC在青光眼中比较小类型的更早死亡。本课题首先通过定量聚合酶链反应（PCR）技术研究了视神经损伤和青光眼模型诱导RGC死亡的BH 3-only蛋白基因。在视神经移植后一天，仅诱导了BH 3-only蛋白信使RNA（mRNA）的一个子集。大部分的BH 3-only蛋白基因的检测没有统计学上的变化，由视神经交易。而玻璃体内注射N-甲基-D-天冬氨酸（N-methyl-D-aspartic acid，N-methyl-D-aspartic acid）则诱导不同类型的BH 3-only蛋白基因的表达。在雪貂视网膜中，RGCs的形态和生理特性及其相关性已被充分研究。在大鼠视网膜中，抗Bim抗体标记视神经切断后的RGCs。在平板视网膜上，我们试图确定哪种类型的RGCs主要表达Bim蛋白。Bim表达细胞的索马大小分布与所有存活的RGCs不同。这是首次报道Bim主要在RGC亚型中诱导。在雪貂视网膜中，还在平板视网膜上研究了Bim表达RGC。我们还证明Bim在RGC亚型中选择性表达。这些结果有力地表明，Bim和其他仅BH 3蛋白有助于在不同的死亡诱导刺激下的亚型特异性RGC死亡。