Determination of treatment modalities for diabetic retinopathy and diabetic maculopathy -Strategic approach using molecular and cellular biological methods-

糖尿病视网膜病变和糖尿病黄斑病变（黄斑水肿）的发病机制涉及多种因素。候选的危险因素是与氧化应激和视网膜血管生成有关的因素。作为研究在糖尿病视网膜病变中发挥重要作用的候选分子的第一步，在获得书面许可后，在糖尿病眼玻璃体中测量氧化应激细胞损伤生物标志物(（8-OHdG和NOx）和细胞因子（VEGF和IL-6）的表达水平。本研究经山形大学医学院伦理委员会批准。本研究揭示了糖尿病视网膜病变和糖尿病黄斑病变与氧化应激和VEGF、IL-6密切相关。第二步，通过将视网膜损伤聚焦到视网膜神经元来探讨糖尿病视网膜病变的分子发病机制，利用体外系统研究了高血糖的细胞内信号转导，包括正常代谢途径和细胞因子表达加速。本研究表明，二酰基甘油激活蛋白激酶C，从而增加视网膜细胞中VEGF的表达。综上所述，VEGF是参与糖尿病视网膜病变和黄斑病变发病的主要因素之一。研究了VEGF基因的单核苷酸多态性（snp）之一。测定108例受试者DNA中VEGF +813 C-T （CC、CT、TT）的频率（非DM=12例，DM=96例）。VEGF +813 C_T多态性在糖尿病组和非糖尿病组的频率相似。视网膜病变的严重程度与VEGF +813多态性无关。本研究结果表明，与糖尿病视网膜病变和黄斑病变相关的不是遗传因素，而是细胞因子和氧化应激相关因子的表达水平。必须寻找与糖尿病视网膜病变和黄斑病变相关的更有用的因素来建立系统，以确定糖尿病视网膜病变和黄斑病变的治疗方式。少

Various factors are involved in the pathogenesis of diabetic retinopathy and diabetic maculopathy (macular edema). The candidates of the risk factors are factors related to oxidative stress and retinal angiogenesis. As the first step, to investigate the candidate molecules to play important roles in diabetic retinopathy, the expression levels of the bio-marker of cell damage due to oxidative stress ((8-OHdG and NOx) and cytokines (VEGF and IL-6) were measured in the vitreous humor obtained from the diabetic eyes after securing the written permission. This study was approved by the ethical committee of Yamagata University Faculty of Medicine. This study has revealed that the diabetic retinopathy and the diabetic maculopathy are closely related to the oxidative stress and VEGF, IL-6. As the second step, to investigate the molecular pathogenesis of diabetic retinopathy by focusing the retinal damage to retinal neurons, the intracellular signal transduction of hyperglycemia, including abno … More rmal metabolic pathways and cytokine expression acceleration, has been investigated using the in vitro systems. This study has revealed that diacylglycerol activates protein kinase C, which increases VEGF expression in retinal cells.Taken together, VEGF is one of the main factors to be involved in the pathogenesis of diabetic retinopathy and maculopathy. One of the single nucleotide polymorphisms (SNPs) in the VEGF gene was investigated. The frequencies of VEGF +813 C-T (CC, CT, TT) were determined in DNA from 108 subjects (non DM=12 subjects, DM=96 subjects). The frequencies of the VEGF +813 C_T polymorphisms were similar in both DM and non DM groups. The severity of retinopathy was not related to VEGF +813 polymorphism. The results of this study have revealed that the expression levels of cytokines and oxidative stress related factors, not the genetic factor were related to diabetic retinopathy and maculopathy. It is mandatory to search for the more useful factors relevant to diabetic retinopathy and maculopathy to set up the system to determine the treatment modalities for diabetic retinopathy and maculopathy. Less