Vascular basement membrane (BM) thickening has been hailed over half a century as the most prominent histological lesion in diabetic microangiopathy, and represents an early ultrastructural change in diabetic retinopathy (DR). Although vascular complications of DR have been clinically well established, specific cellular and molecular mechanisms underlying dysfunction of small vessels are not well understood. In DR, small vessels develop insidiously as BM thickening occurs. Studies examining high resolution imaging data have established BM thickening as one of the foremost structural abnormalities of retinal capillaries. This fundamental structural change develops, at least in part, from excess accumulation of BM components. Although BM thickening is closely associated with the development of DR, its contributory role in the pathogenesis of DR is coming to light recently. DR develops over several years before clinical manifestations appear, and it is during this clinically silent period that hyperglycemia induces excess synthesis of BM components, contributes to vascular BM thickening, and promotes structural and functional lesions including cell death and vascular leakage in the diabetic retina. Studies using animal models show promising results in preventing BM thickening with subsequent beneficial effects. Several gene regulatory approaches are being developed to prevent excess synthesis of vascular BM components in an effort to reduce BM thickening. This review highlights current understanding of capillary BM thickening development, role of BM thickening in retinal vascular lesions, and strategies for preventing vascular BM thickening as a potential therapeutic strategy in alleviating characteristic lesions associated with DR.

半个多世纪以来，血管基底膜 (BM) 增厚被誉为糖尿病微血管病变中最突出的组织学病变，代表了糖尿病视网膜病变 (DR) 的早期超微结构变化。尽管 DR 的血管并发症已在临床上得到充分证实，但小血管功能障碍的特定细胞和分子机制尚不清楚。在 DR 中，随着 BM 增厚，小血管会隐匿地发展。检查高分辨率成像数据的研究已确定 BM 增厚是视网膜毛细血管最重要的结构异常之一。这种根本性的结构变化至少部分是由于 BM 成分的过度积累而产生的。尽管 BM 增厚与 DR 的发展密切相关，它在 DR 发病机制中的作用最近才逐渐显现。DR 在临床表现出现之前已经发展了数年，并且正是在这个临床静默期，高血糖诱导 BM 成分的过量合成，导致血管 BM 增厚，并促进糖尿病视网膜中的结构和功能损伤，包括细胞死亡和血管渗漏。使用动物模型的研究表明，在预防 BM 增厚方面取得了可喜的结果，并产生了随后的有益效果。正在开发几种基因调控方法来防止血管 BM 成分的过度合成，以减少 BM 增厚。这篇综述强调了目前对毛细血管 BM 增厚发展的认识，BM 增厚在视网膜血管病变中的作用，