Connexin 43 (Cx43) Regulates High-glucose-induced Retinal Endothelial Cell Angiogenesis and Retinal Neovascularization
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Diabetic retinopathy (DR) is an important microvascular complication of type 1 and type 2 diabetes mellitus (DM) and a major cause of blindness. Retinal neovascularization plays a critical role in the proliferative DR. In this study, high glucose-induced connexin 43 (Cx43) expression in human retinal endothelial cells (hRECs) in a dose-dependent manner. Compared with hRECs under normal culture conditions, high-glucose (HG)-stimulated hRECs showed promoted tubule formation, increased ROS release, and elevated levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), vascular endothelial growth factor A (VEGFA), and intercellular adhesion molecule 1 (ICAM-1) in the culture medium. HG-induced alterations were further magnified after overexpression, whereas partially eliminated after knockdown. Finally, in the DR mouse model, impaired retinal structure, increased CD31 expression, and elevated mRNA levels of , , , and were observed; knockdown partially reversed these phenomena. Conclusively, knockdown could inhibit hREC angiogenesis, therefore improving DR in the mouse model.
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