MicroRNA-143 plays a protective role in ischemia-induced retinal neovascularization

Abstract Retinal neovascularization is a severe complication of proliferative diabetic retinopathy. MicroRNAs (miRNAs) are master regulators of gene expression that play important roles in retinal neovascularization. Here, we investigated the retinal miRNA expression profile in a rat model of oxygen-induced retinopathy (OIR) through miRNA-Seq. We found that miR-143-3p, miR-126-3p, miR-150-5p and miR-145-5p were significantly down-regulated in the retina of OIR rats, and directly involved in the development of retinal neovascularization. Of these identified miRNAs, miR-143 is enriched in retina and was first reported being associated with pathological retinal angiogenesis. Our RNA-Seq data further suggested that miR-143 alleviates retinal neovascularization by mediating the inflammation/stress pathways via Fos . Moreover, the computational analysis indicated that Transforming Growth Factor-beta Activated Kinase 1 ( TAK1 ) is involved in several key pathways associated with the dysregulated miRNAs. The pharmacological inhibition of TAK1 suppressed angiogenesis in vitro and retinal neovascularization in vivo . Our data highlight the utility of next-generation sequencing in the development of therapeutics for ocular neovascularization and further suggest that therapeutic targeting the dysregulated miRNAs or TAK1 may be a feasible adjunct therapeutic approach in patients with retinal neovascularization.