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Molecular biological investigation to prohibit the initiation and progression of diabetic retinopathy.

阻止糖尿病视网膜病变发生和进展的分子生物学研究。

基本信息

批准号：
09470382
负责人：
ISHIBASHI Tatsuro
金额：
$ 5.12万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-09470382/
关键词：
diabetic retinopathy VEGF VPF AGEs hypoxia glia Bucillamine 糖尿病網膜症網膜網膜血管組織因子 in vitro AGE グリア細胞 in vivo

项目摘要

Diabetic retinopathy (DR), which is characterized by gradually progressive alterations in che retinal microvasculature, still remains the leading cause of blindness in the working population. Consequently, further investigation of the pathogenesis of DR is necessary to develop the better therapeutical strategy to prohibit the initiation and progression of DR.Recent studies revealed that vascular endothelial growth factor (VEGF) also known as vascular permeability factor (VPF) is involved in the pathogenesis of DR.Thus, VEGF is considered to be a possible molecular target for the treatment of DR.We identified the significant correlation between the accumulation of advanced glycation endproducts (AGEs) and VEGF expression in diabetic retinal tissue. In vitro. AGEs stimulated not only VEGF gene expression by cutured retinal glial cells but also the expression of KDR gene, which is a major VEGF receptor, by cultured retinal capillary endothelial cells. Thus, AGEs appeared to be one of the major stimuli activating VEGF and its receptor system in diabetic retinal tissue.Intravitreal injection of AGEs caused retinal vascular hyperpermeability in rat eyes possibly through the activation of VEGF and its receptor system. Intraperitoneal injection of Bucillamine, which is one of the anti-rheumatic drugs, inhibited AGEs-dependent retinal vascular hyperpermeability. Furtheremore, Bucillamine prohibited hypoxia-induced VEGF gene expression by cultured retinal glial cells. These results indicated that Bucillamine might be therapeutically useful for DR through the downregulation of VEGF and its receptor system.

糖尿病视网膜病变（diabetic retinopathy，DR）是一种以视网膜微血管病变为特征的渐进性疾病，目前仍是工作人群致盲的主要原因。因此，有必要进一步研究DR的发病机制，以开发更好的治疗策略来阻止DR的发生和发展。最近的研究表明，血管内皮生长因子（VEGF）也称为血管通透性因子（VPF）参与DR的发病机制。VEGF被认为是治疗DR的一个可能的分子靶点。糖尿病视网膜组织中VEGF的表达。体外AGEs不仅刺激培养的视网膜胶质细胞表达VEGF基因，而且刺激培养的视网膜毛细血管内皮细胞表达VEGF的主要受体KDR基因。AGEs可能是糖尿病视网膜组织中激活VEGF及其受体系统的主要刺激物之一，玻璃体内注射AGEs可能通过激活VEGF及其受体系统引起大鼠视网膜血管通透性增高。抗风湿药布西拉明腹腔注射可抑制AGEs依赖性视网膜血管通透性增高。此外，布西拉明抑制缺氧诱导的视网膜神经胶质细胞VEGF基因表达。这些结果表明，布西拉明可能是通过下调VEGF及其受体系统治疗DR。