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.

众所周知，有几种亚型的视网膜神经节细胞（RGC），其躯体大小，树突形态和电生理特性区分了。视神经交易后，较小类型的RGC主要死亡。相比之下，与较小的类型相比，青光眼中较大类型的RGC在青光眼中死亡。然而，尚不清楚亚型特异性RGC死亡的分子机制。在该项目中，我们首先试图通过定量聚合酶链反应（PCR）确定通过视神经交易和青光眼模型诱导哪种类型的仅BH3蛋白基因。视神经交易后的一天，仅诱导仅BH3蛋白质信使RNA（mRNA）的子集。检查的大多数仅BH3蛋白基因没有通过视神经交易在统计上改变。相比之下，vitreal注入N-甲基-D-天冬氨酸（一种青光眼模型）诱导了不同类型的仅BH3纯蛋白基因。NEXT，通过免疫组织化学研究了视神经透射大鼠和雪貂视网膜的BIM蛋白表达。在雪貂视网膜中，对RGC的形态和生理特性及其相关性进行了充分的研究。在大鼠视网膜中，抗BIM抗体在视神经横向后标记RGC。在Flatmount Retina上，我们试图确定哪种类型的RGC主要表达BIM蛋白。 BIM表达细胞的SOMA尺寸分布与所有存活的RGC不同。这是第一个报告BIM主要是在RGC的亚型中引起的。在雪貂视网膜中，还对表达RGC的BIM进行了研究。我们还证明了BIM在RGC的亚型中有选择地表达。这些结果强烈表明，BIM和其他仅BH3蛋白在不同死亡诱导刺激的情况下导致亚型特异性RGC死亡。