YAP1 inhibition protects retinal vascular endothelial cells under high glucose by inhibiting autophagy

Diabetic retinopathy (DR) is a frequent diabetes-associated microvascular disorder, and its underlying mechanism of pathogenesis remains unclear. Previous studies have suggested that YAP1 is involved in endothelial activation and vascular inflammation. In the present study, we explored the biological role of YAP1 in retinal vascular endothelial cells (RVECs) in response to high glucose (HG). YAP1 expression was first evaluated in retinal endothelial cells cultured with HG. In retinal endothelial cells, the consequences of HG exposure and the alteration of YAP1 expression were systematically evaluated, focusing on cell growth, survival, tube formation, migration, and activation of autophagy. To further evaluate the protective effect of YAP1 inhibition on retinal endothelial cells in vivo, a streptozocin-induced DR mouse model was employed. First, we discovered that YAP1 expression was dose-dependently elevated under glucose treatment in retinal endothelial RF/6A and human primary retinal endothelial cells. Accordingly, suppression of YAP1 exhibited a protective role in HG-treated retinal endothelial cells by decreasing cell viability and suppressing apoptotic deaths. Moreover, inhibition of YAP1 impairs migration and tube formation of retinal cells and alleviates autophagy in response to HG. Additionally, YAP1 knockdown reversed glucose-induced nucleus translocation of NF-κB. This study demonstrated that inhibition of YAP1 exhibits a protective role against HG-induced RVEC injury, representing a novel target for the management and therapy of DR in clinics.