The potential protective effects of miR-497 on corneal neovascularization are mediated via macrophage through the IL-6/STAT3/VEGF signaling pathway

Corneal neovascularization (CoNV) can cause abnormal blood vessels to grow in the transparent cornea, leading to various sight-threatening eye diseases. MicroRNAs are known to play essential roles in the regulation of numerous biological functions. We try to clarify the role of a specific microRNA, miR‑497, which has been shown to regulate the growth of tumor cells and angiogenesis on the basis of available data. However, the association between miR-497 and vascularized cornea remains unclear. Therefore, it is urgently needed to understand the molecular mechanism of miR497 in the progress of corneal neovascularization. Animal model of CoNV was established in wildtype (WT) C57BL/6 mice, CRISPR/Cas9 mediated miR-497 knockout (KO) and overexpressed (TG) C57BL/6 mice. MiR-497, expressed in corneas, was actively involved in alkali burn-induced corneal neovascularization via targeting STAT3 and negatively regulating its expression, attenuating macrophage infiltration and M2 polarization. Knockdown of miR-497 enhanced the formation of corneal angiogenesis through targeting STAT3 and facilitating its expression, promoting recruitment of macrophages, while overexpression of miR-497 restrained blood vessel sprouting via regulating downstream STAT3 and VEGFA expression, reducing macrophage activation and inhibiting M2 polarization. Moreover, miR-497 knockout-mediated damage effect can be rescued through the inhibition of STAT3 signaling. Mechanically, miR-497 might serve as a potential strategy for pathological corneal neovascularization via macrophage through the IL-6/STAT3/VEGFA signaling pathway.