AUTHOR=Shi Wen , Meng Zhishang , Luo Jing 

TITLE=Connexin 43 (Cx43) regulates high-glucose-induced retinal endothelial cell angiogenesis and retinal neovascularization

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.909207

DOI=10.3389/fendo.2022.909207

ISSN=1664-2392

ABSTRACT=<p>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 <italic>Cx43</italic> overexpression, whereas partially eliminated after <italic>Cx43</italic> knockdown. Finally, in the DR mouse model, impaired retinal structure, increased CD31 expression, and elevated mRNA levels of <italic>TNF-α</italic>, <italic>IL-1β</italic>, <italic>VEGFA</italic>, and <italic>ICAM-1</italic> were observed; <italic>in-vivo Cx43</italic> knockdown partially reversed these phenomena. Conclusively, <italic>Cx43</italic> knockdown could inhibit hREC angiogenesis, therefore improving DR in the mouse model.</p>