Retinal capillary basement membrane thickening: Role in the pathogenesis of diabetic retinopathy.
Retinal capillary basement membrane thickening: Role in the pathogenesis of diabetic retinopathy.
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DOI：
10.1016/j.preteyeres.2020.100903
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发表时间：
2021-05
影响因子：
17.8
通讯作者：
Kim D
中科院分区：
文献类型：
--
作者：
Roy S;Kim D
半个多世纪以来，血管基底膜（BM）增厚被认为是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）的早期超微结构改变。虽然DR的血管并发症在临床上已经得到了很好的证实，但小血管功能障碍的具体细胞和分子机制还没有得到很好的理解。在DR中，随着BM增厚，小血管不知不觉地发展。检查高分辨率成像数据的研究已经确定BM增厚是视网膜毛细血管最重要的结构异常之一。这种基本的结构变化至少部分是由于BM组分的过量积累而产生的。虽然BM增厚与DR的发生密切相关，但其在DR发病机制中的作用近年来逐渐被人们所认识。在临床表现出现之前，DR发展了数年，并且正是在该临床沉默期期间，高血糖诱导BM组分的过量合成，促成血管BM增厚，并促进结构和功能性病变，包括糖尿病视网膜中的细胞死亡和血管渗漏。使用动物模型的研究显示了预防BM增厚的有希望的结果，随后具有有益的效果。正在开发几种基因调控方法来防止血管BM组分的过度合成，以减少BM增厚。这篇综述强调了目前对毛细血管BM增厚发展的理解，BM增厚在视网膜血管病变中的作用，以及预防血管BM增厚作为缓解DR相关特征性病变的潜在治疗策略的策略。
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.
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影响因子：
4.1
作者：
ASHTON, N
通讯作者：
ASHTON, N
影响因子：
2
作者：
Bollineni, JS;Alluru, I;Reddi, AS
通讯作者：
Reddi, AS
影响因子：
8.2
作者：
Beltramo, E;Buttiglieri, S;Porta, M
通讯作者：
Porta, M
DOI：
10.1111/j.1432-1033.1989.tb15013.x
发表时间：
1989-09-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
AUMAILLEY, M;WIEDEMANN, H;TIMPL, R
通讯作者：
TIMPL, R
影响因子：
7.7
作者：
Antonetti, DA;Barber, AJ;Gardner, TW
通讯作者：
Gardner, TW