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

糖尿病视网膜病变(DR)的特征是视网膜微血管的渐进性改变，它仍然是导致工作人群失明的主要原因。因此，有必要对DR的发病机制进行进一步的研究，以制定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)也被称为血管渗透因子(VPF)参与了DR的发病机制，因此，VEGF被认为是治疗DR的一个可能的分子靶点。在试管中。AGEs不仅能刺激培养的视网膜胶质细胞表达血管内皮生长因子基因，而且还能刺激培养的视网膜毛细血管内皮细胞表达主要的血管内皮生长因子受体KDR基因。因此，AGEs可能是糖尿病大鼠视网膜组织中激活血管内皮生长因子及其受体系统的主要刺激物之一。玻璃体内注射AGEs可能通过激活血管内皮生长因子及其受体系统而导致大鼠视网膜血管通透性增高。腹腔注射抗风湿药物布希拉明可抑制AGEs依赖的视网膜血管高通透性。此外，布地拉明可抑制低氧诱导的视网膜神经胶质细胞表达血管内皮生长因子基因。提示布比拉明可能通过下调血管内皮细胞生长因子及其受体系统对糖尿病视网膜病变有治疗作用。

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.