Roy Sayon, Jiang Jean X, Li An-Fei, Kim Dongjoon
Departments of Medicine and Ophthalmology, Boston University School of Medicine, Boston, MA, United States.
Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX, United States.
Prog Retin Eye Res. 2017 Nov;61:35-59. doi: 10.1016/j.preteyeres.2017.06.001. Epub 2017 Jun 8.
Diabetic retinopathy is the leading cause of blindness in the working age population. Unfortunately, there is no cure for this devastating ocular complication. The early stage of diabetic retinopathy is characterized by the loss of various cell types in the retina, namely endothelial cells and pericytes. As the disease progresses, vascular leakage, a clinical hallmark of diabetic retinopathy, becomes evident and may eventually lead to diabetic macular edema, the most common cause of vision loss in diabetic retinopathy. Substantial evidence indicates that the disruption of connexin-mediated cellular communication plays a critical role in the pathogenesis of diabetic retinopathy. Yet, it is unclear how altered communication via connexin channel mediated cell-to-cell and cell-to-extracellular microenvironment is linked to the development of diabetic retinopathy. Recent observations suggest the possibility that connexin hemichannels may play a role in the pathogenesis of diabetic retinopathy by allowing communication between cells and the microenvironment. Interestingly, recent studies suggest that connexin channels may be involved in regulating retinal vascular permeability. These cellular events are coordinated at least in part via connexin-mediated intercellular communication and the maintenance of retinal vascular homeostasis. This review highlights the effect of high glucose and diabetic condition on connexin channels and their impact on the development of diabetic retinopathy.
糖尿病视网膜病变是劳动年龄人群失明的主要原因。不幸的是,这种毁灭性的眼部并发症无法治愈。糖尿病视网膜病变的早期特征是视网膜中各种细胞类型的丧失,即内皮细胞和周细胞。随着疾病进展,血管渗漏这一糖尿病视网膜病变的临床标志变得明显,并最终可能导致糖尿病性黄斑水肿,这是糖尿病视网膜病变中视力丧失的最常见原因。大量证据表明,连接蛋白介导的细胞通讯破坏在糖尿病视网膜病变的发病机制中起关键作用。然而,尚不清楚通过连接蛋白通道介导的细胞间和细胞与细胞外微环境之间的通讯改变如何与糖尿病视网膜病变的发展相关联。最近的观察结果提示,连接蛋白半通道可能通过允许细胞与微环境之间的通讯而在糖尿病视网膜病变的发病机制中发挥作用。有趣的是,最近的研究表明连接蛋白通道可能参与调节视网膜血管通透性。这些细胞事件至少部分地通过连接蛋白介导的细胞间通讯和视网膜血管稳态的维持来协调。本综述重点介绍高血糖和糖尿病状态对连接蛋白通道的影响及其对糖尿病视网膜病变发展的影响。