University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, K1Y 4W7, Canada.
Amino Acids. 2013 Jun;44(6):1397-407. doi: 10.1007/s00726-011-1071-3. Epub 2011 Sep 11.
Retinopathy is a serious microvascular complication of diabetes and a major cause of blindness in young adults, worldwide. Early diabetic retinopathy is characterized by a loss of pericytes from retinal capillaries, the appearance of acellular capillaries and microaneurysms, and a breakdown of the blood-retinal barrier. In later stages, this can evolve into the proliferative phase in which there is neovascularization of the retina, which greatly increases the probability of vision loss. Advanced glycation end products (AGEs) which accumulate under hyperglycemic conditions are thought to play an important role in the pathogenesis of diabetic retinopathy. AGEs arise primarily by the modification of amine groups of proteins by reactive dicarbonyls such as methylglyoxal. Intracellular proteins including anti-oxidant enzymes, transcription factors and mitochondrial proteins are targets of dicarbonyl modification and this can modify their functional properties and thus compromise cellular physiology. Likewise, modification of extracellular proteins by dicarbonyls can impair cell adhesion and can generate ligands that can potentially bind to cell surface AGE receptors that activate pro-inflammatory signaling pathways. AGE inhibitors have been shown to provide protection in animal models of diabetic retinopathy and currently are being evaluated in clinical trials.
糖尿病性视网膜病变是一种严重的微血管并发症，也是全球范围内导致年轻人失明的主要原因。早期糖尿病性视网膜病变的特征是视网膜毛细血管周细胞丧失、无细胞毛细血管和微动脉瘤出现，以及血视网膜屏障破裂。在后期，这可能演变为增生期，此时视网膜会出现新生血管，这大大增加了视力丧失的可能性。在高血糖条件下积累的晚期糖基化终产物（AGEs）被认为在糖尿病性视网膜病变的发病机制中起重要作用。AGEs 主要通过活性二羰基如甲基乙二醛修饰蛋白质的胺基而产生。包括抗氧化酶、转录因子和线粒体蛋白在内的细胞内蛋白是二羰基修饰的靶标，这会改变它们的功能特性，从而损害细胞生理功能。同样，二羰基修饰细胞外蛋白会损害细胞黏附，并能产生潜在的与细胞表面 AGE 受体结合的配体，激活促炎信号通路。AGE 抑制剂已被证明在糖尿病性视网膜病变的动物模型中具有保护作用，目前正在临床试验中进行评估。
