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[视网膜变性与再生机制的阐明及其临床应用前景]

[Elucidation of the mechanism of retinal degeneration and regeneration and the prospects for its clinical application].

作者信息

Kajiwara K, Okanao E, Kaneko Y, Shinozaki H, Shooter E M, Takahashi N, Hida T, Hirakata A, Fukuda M

机构信息

Department of Neurobiology, Stanford University School of Medicine, USA.

出版信息

Nippon Ganka Gakkai Zasshi. 1997 Dec;101(12):987-1000.

PMID:9436360
Abstract

In order to obtain the basic knowledge necessary to develop therapeutical intervention for blindness due to the damaged retina and optic nerve, the mechanism of retinal degeneration and regeneration in an amphibian model, Cynops pyrrhogaster, was studied. In the retinal degenerative process following enucleation and reimplantation of the eye ball, evidence was found for active cell death of neural retinal cells. As the degeneration proceeded, Musashi, an ribonucleic acid (RNA)-binding protein, started its expression in the daughter cells of proliferating retinal pigment epithelium (RPE) cells, messenger RNA (mRNA) expression of proneural genes with basic helix-loop-helix motif was then detected in the newly developing retina. These results suggest that transdifferentiation of RPE cells to neural retina involves at least partial cascade, if not entirely, of neural induction from uncommitted ectodermal tissue. Search for genes that are required for transdifferentiation of RPE cells to neural retinal cells, in addition to those mentioned above, will provide the basic knowledge for successful retinal transplantation and retinal regeneration in higher vertebrates.

摘要

为了获取开发针对视网膜和视神经损伤所致失明的治疗干预措施所需的基础知识,对一种两栖动物模型——日本大鲵(Cynops pyrrhogaster)视网膜变性和再生的机制进行了研究。在眼球摘除和再植入后的视网膜变性过程中,发现了神经视网膜细胞主动死亡的证据。随着变性的进展,一种核糖核酸(RNA)结合蛋白Musashi开始在增殖的视网膜色素上皮(RPE)细胞的子代细胞中表达,随后在新发育的视网膜中检测到具有碱性螺旋-环-螺旋基序的神经前体基因的信使核糖核酸(mRNA)表达。这些结果表明,RPE细胞向神经视网膜的转分化至少涉及(如果不是完全涉及)来自未分化外胚层组织的神经诱导的部分级联反应。除上述基因外,寻找RPE细胞向神经视网膜细胞转分化所需的基因,将为高等脊椎动物成功进行视网膜移植和视网膜再生提供基础知识。

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