Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA 30912, United States; James and Jean Culver Vision Discovery Institute, Augusta University, Augusta, GA 30912, United States.
Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA 30912, United States; Vascular Biology Center, Augusta University, Augusta, GA 30912, United States; James and Jean Culver Vision Discovery Institute, Augusta University, Augusta, GA 30912, United States.
Pharmacol Res. 2020 Nov;161:105115. doi: 10.1016/j.phrs.2020.105115. Epub 2020 Aug 1.
Loss of the blood-retinal barrier (BRB) integrity and subsequent damage to the neurovascular unit in the retina are the underlying reasons for diabetic retinopathy (DR). Damage to BRB eventually leads to severe visual impairment in the absence of prompt intervention. Diabetic macular edema and proliferative DR are the advanced stages of the disease where BRB integrity is altered. Primary mechanisms contributing to BRB dysfunction include loss of cell-cell barrier junctions, vascular endothelial growth factor, advanced glycation end products-induced damage, and oxidative stress. Although much is known about the involvement of adherens and tight-junction proteins in the regulation of vascular permeability in various diseases, there is a significant gap in our knowledge on the junctional proteins expressed in the BRB and how BRB function is modulated in the diabetic retina. In this review article, we present our current understanding of the molecular composition of BRB, the changes in the BRB junctional protein turnover in DR, and how BRB functional modulation affects vascular permeability and macular edema in the diabetic retina.
血视网膜屏障 (BRB) 完整性的丧失以及随后视网膜中神经血管单元的损伤是糖尿病性视网膜病变 (DR) 的根本原因。BRB 的损伤最终会导致严重的视力损害，如果不及时干预的话。糖尿病性黄斑水肿和增生性 DR 是疾病的晚期阶段，BRB 完整性发生改变。导致 BRB 功能障碍的主要机制包括细胞-细胞屏障连接的丧失、血管内皮生长因子、晚期糖基化终产物诱导的损伤和氧化应激。尽管我们对各种疾病中黏附连接和紧密连接蛋白在调节血管通透性中的作用有了很多了解，但我们对 BRB 中表达的连接蛋白以及 BRB 功能如何在糖尿病视网膜中调节的了解还存在很大的差距。在这篇综述文章中，我们介绍了对 BRB 的分子组成、DR 中 BRB 连接蛋白周转的变化以及 BRB 功能调节如何影响糖尿病视网膜中的血管通透性和黄斑水肿的现有认识。
