Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions
Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions
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DOI：
10.1016/j.preteyeres.2013.02.001
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发表时间：
2013-05-01
影响因子：
17.8
通讯作者：
Schlingemann, Reinier O.
中科院分区：
文献类型：
--
作者：
Klaassen, Ingeborg;Van Noorden, Cornelis J. F.;Schlingemann, Reinier O.
糖尿病视网膜病变、老年性黄斑变性、视网膜静脉阻塞、葡萄膜炎和其他慢性视网膜疾病都会引起内皮细胞血-视网膜屏障(BRB)的破坏，导致血管源性水肿和神经组织损伤，导致视力丧失。BRB功能改变的中心机制是由于生长因子、细胞因子、晚期糖基化终产物、炎症、高血糖和周细胞丢失水平的升高而导致视网膜内皮细胞通透性的改变。随后，通过内皮细胞间连接的开放和内皮小窝跨细胞运输的质和量的变化，视网膜血管壁的细胞旁运输和跨细胞运输分别增加。周细胞和星形胶质细胞的功能变化，以及内皮细胞糖萼和BRB内皮周围的基底膜的结构变化，进一步促进了BRB的渗漏。根据Starling规则，BRB内皮细胞主动跨细胞转运血浆蛋白，导致间质渗透压升高，可能是黄斑水肿形成的主要因素。近年来，人们对BRB泄漏所涉及的复杂细胞和分子过程的了解迅速增长。尽管缺乏针对糖尿病黄斑水肿等人类疾病的适当动物模型，但这些见解为合理设计旨在恢复BRB的药物以及设计有效地跨越BRB的药物输送提供了工具，以治疗影响数百万患者生活质量的慢性视网膜疾病，如糖尿病黄斑水肿。(C)2013爱思唯尔有限公司。保留所有权利。
Breakdown of the inner endothelial blood-retinal barrier (BRB), as occurs in diabetic retinopathy, age-related macular degeneration, retinal vein occlusions, uveitis and other chronic retinal diseases, results in vasogenic edema and neural tissue damage, causing loss of vision. The central mechanism of altered BRB function is a change in the permeability characteristics of retinal endothelial cells caused by elevated levels of growth factors, cytokines, advanced glycation end products, inflammation, hyperglycemia and loss of pericytes. Subsequently, paracellular but also transcellular transport across the retinal vascular wall increases via opening of endothelial intercellular junctions and qualitative and quantitative changes in endothelial caveolar transcellular transport, respectively. Functional changes in pericytes and astrocytes, as well as structural changes in the composition of the endothelial glycocalyx and the basal lamina around BRB endothelium further facilitate BRB leakage. As Starling's rules apply, active transcellular transport of plasma proteins by the BRB endothelial cells causing increased interstitial osmotic pressure is probably the main factor in the formation of macular edema. The understanding of the complex cellular and molecular processes involved in BRB leakage has grown rapidly in recent years. Although appropriate animal models for human conditions like diabetic macular edema are lacking, these insights have provided tools for rational design of drugs aimed at restoring the BRB as well as for design of effective transport of drugs across the BRB, to treat the chronic retinal diseases such as diabetic macular edema that affect the quality-of-life of millions of patients. (C) 2013 Elsevier Ltd. All rights reserved.