Targeting pericyte-expressed circ_0001186 for the inhibitionof diabetes-induced retinal vascular dysfunction

Abstract

Pericytes play important roles in retinal vascular mature and homeostasis. Their dysfunction is apathological manifestation in diabetes retinopathy. Circular RNAs have emerged as a class of regulatory RNA tran‐scripts and are involved in the regulation of several physiological and pathological processes. In this study, diabe‐tes-related stresses led to increased expression of circ_0001186 in pericytes but had no effects on the expression ofcirc_0001186 in endothelial cells. In vitro studies showed that circ_0001186 knockdown reduced high glucose-in‐duced pericyte injury, contributed to the proliferation of pericytes and the recruitment of pericytes to endothelialcells. In vivo studies showed that conditional knockdown of circ_0001186 in pericytes decreased diabetes-inducedpericyte loss, suppressed retinal vascular leak and inflammatory response. Mechanistically, knockdown of circ_0001186 could activate PDGF-PI3K-Akt signaling and protect pericytes against high glucose-induced injury. Thisstudy revealed a novel mechanism of retinal vascular dysfunction. Targeting of pericyte-expressed circ_0001186provides a novel insight into the treatment of diabetes retinopathy.

Keywords

• pericyte
• diabetes retinopathy
• circular rna
• pdgf-pi3k-akt signaling pathway