Connexin channel and its role in diabetic retinopathy

Abstract

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.

Chloroquine differentially modulates coronary vasodilation in control and diabetic mice

“…EDH‐dependent relaxation can also be induced by releasing EDHFs (e.g., EETs, H 2 O 2 , and anandamide). We and other investigators demonstrate that the activity of endothelial gap junction is attenuated in diabetes (Makino et al, ; Makino et al, ; Roy, Jiang, Li, & Kim, ). Figure k demonstrates that pretreatment of 18GA (a gap junction inhibitor) significantly inhibits chloroquine‐induced augmentation of EDH‐dependent vascular relaxation in diabetic mice.…”

Gap junction-mediated cell-to-cell communication in oral development and oral diseases: a concise review of research progress

“…18 In vertebrates, the corresponding genes are denominated with a symbol beginning with "GJ" (for gap junction), which represents a virtual narrow separation of 2-4 nm between two neighbouring cells observed using a transmission electron microscope (TEM). 19 Meanwhile, the proteins are generally referred to with an abbreviation beginning with "Cx" (for connexin) combined with a number corresponding to the approximate molecular mass of the predicted polypeptide in kilodaltons (kDa). 20 Structure and function of the connexin hemichannel Structure of connexins.…”

Retinal Cell Protection in Ocular Excitotoxicity Diseases. Possible Alternatives Offered by Microparticulate Drug Delivery Systems and Future Prospects

“…Inferior up-regulation that results in excessive gap junction communication or uncontrolled opening of hemichannels that contribute to "center-surround" antagonism allow pro-inflammatory mediators activation, vascular permeability or interferences between intercellular transfer of ions and metabolites, ending in loss of RGC. Furthermore, it enables the release of apoptotic and necrotic signals from injured cells to the extracellular matrix where death signals can be passed to adjacent cells [37,84,85].…”