MicroRNA-499-3p inhibits proliferation and promotes apoptosis of retinal cells in diabetic retinopathy through activation of the TLR4 signaling pathway by targeting IFNA2.

Abstract

microRNAs (miRNAs) are involved in the physiological and pathophysiological processes of diabetes and its microvascular and macrovascular complications. Hence, the aim of the study was to investigate whether miR-499-3p played an important role in diabetic retinopathy. Diabetic retinopathy was developed in rats by intraperitoneal injection of streptozocin (STZ), followed by collection of retinal tissues and preparation of retinal cells. Immunohistochemical staining was used to detect expression of interferon alpha 2 (IFNA2). RT-qPCR was used to determine the expression of miR-499-3p. Bioinformatics website and dual luciferase reporter gene assay were used to validate the targeting relationship between miR-499-3p and IFNA2. Gain- and loss-of-function assays were performed to explore the functional roles of aberrantly expressed miR-499-3p and IFNA2 in retinal cell proliferation by MTT, and apoptosis by flow cytometry. In retinal tissues and cells of diabetic rats, IFNA2 expression was reduced, and miR-499-3p expression increased to activate the toll-like receptor 4 (TLR4) signaling pathway. IFNA2 was a target gene of miR-499-3p and negatively regulated by miR-499-3p. Further, downregulated miR-499-3p promoted retinal cell proliferation while suppressing apoptosis to alleviate diabetic retinopathy. All in all, miR-499-3p promoted retinopathy by enhancing activation of the TLR4 signaling pathway, which provides a new therapeutic target for diabetic retinopathy.