1809-LB: Hyperglycemia Activated the STING Pathway to Induce Retinal Vascular Endothelial Inflammation and Breakdown of Retinal Tight Junctions

Introduction & Objective: Diabetic retinopathy is a common microvascular complications of diabetes mellitus characterized by hyperglycemia and chronic inflammation. Retinal endothelial cells are the primary target cells for diabetes-induced vascular damage causing acellular blood capillary and capillary leakage in clinical observation. This study investigated the role of the stimulator of interferon genes (STING) signaling pathway in human retinal vascular endothelial cells (HRVEC) damage and inflammation under the condition of hyperglycemia. Methods: HRVEC were treated with Methylglyoxal (MGO), a mimic of hyperglycemia condition. Moreover, we investigated the role of STING in HRVEC by generating a STING-deficient HRVEC using the CRISPR/Cas9 system. The components of the STING signaling pathway and endothelial cell tight junctions at protein levels were determined by Western blotting. Last, RT-qPCR was used for detecting the genes expression of pro-inflammatory cytokines in HRVEC and STING-deficient HRVEC. All those treatment and methods were repeated in the STING siRNA-treated HRVEC. Results: When treated with MGO, the protein levels of the STING signaling components were increased in a time- and dose-manner, suggesting the activation of the STING pathway, accompany by down-regulation of endothelial cell tight junction protein and increased transcription levels of inflammatory genes. At the same time, the increased transcription levels of inflammation genes and decreased expression levels of tight junction proteins caused by MGO were significantly repressed when the STING gene was deleted or knocked down in HRVEC. Conclusion: STING deficiency can significantly inhibit the expression of proinflammatory factors in HRVEC, also improving the HRVEC damages induced by MGO.