Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, China.
Department of Blood Transfusion, The Second Hospital of Jilin University, Changchun, China.
Clin Exp Pharmacol Physiol. 2020 Jan;47(1):85-94. doi: 10.1111/1440-1681.13163. Epub 2019 Oct 7.
Proliferative diabetic retinopathy (PDR) is a common complication of diabetes mellitus, characterized by abnormal retinal angiogenesis. MicroRNA-203-3p (miR-203-3p) was found to be down-regulated in a murine model of proliferative retinopathy. This study was performed to explore the role of miR-203a-3p in retinal angiogenesis of PDR. Firstly, a rat OIR model, which was used to mimic PDR, was established and the OIR rats were treated with scrambled control or miR-203a-3p agomir by intravitreal injection. The results showed that the level of miR-203a-3p was decreased in OIR rats, and forced over-expression of miR-203a-3p inhibited OIR-induced retinal angiogenesis as evidenced by reduced blood vessel profiles and CD31 expression. OIR-induced up-regulation of VEGFA, HIF-α, PCNA, and MMPs in the retina was also counteracted by miR-203a-3p. Additionally, high glucose (HG)-induced proliferation, migration and tube formation of human retinal microvascular endothelial cells (HRMECs) were also dampened by the up-regulation of miR-203a-3p. Dual-luciferase reporter assay showed that miR-203a-3p could specifically bind to the 3'UTR of VEGFA and HIF-1α. Over-expression of VEGFA or HIF-1α restored the tube formation activity of HRMECs suppressed by miR-203a-3p. In conclusion, our findings demonstrate that up-regulation of miR-203a-3p might inhibit pathological retinal angiogenesis of PDR by targeting VEGFA and HIF-1α.
增生性糖尿病视网膜病变（PDR）是糖尿病的常见并发症，其特征是视网膜异常血管生成。在增生性视网膜病变的小鼠模型中发现 microRNA-203-3p（miR-203-3p）下调。本研究旨在探讨 miR-203a-3p 在 PDR 视网膜血管生成中的作用。首先，建立了模拟 PDR 的大鼠 OIR 模型，并通过玻璃体腔内注射将 scrambled 对照或 miR-203a-3p agomir 处理 OIR 大鼠。结果表明，OIR 大鼠中 miR-203a-3p 水平降低，强制过表达 miR-203a-3p 抑制 OIR 诱导的视网膜血管生成，表现为血管形态和 CD31 表达减少。OIR 诱导的视网膜中 VEGFA、HIF-α、PCNA 和 MMPs 的上调也被 miR-203a-3p 逆转。此外，miR-203a-3p 的上调还抑制了高糖（HG）诱导的人视网膜微血管内皮细胞（HRMEC）的增殖、迁移和管形成。双荧光素酶报告基因检测表明，miR-203a-3p 可以特异性结合 VEGFA 和 HIF-1α 的 3'UTR。过表达 VEGFA 或 HIF-1α 恢复了 miR-203a-3p 抑制的 HRMEC 管形成活性。总之，我们的研究结果表明，上调 miR-203a-3p 可能通过靶向 VEGFA 和 HIF-1α 抑制 PDR 的病理性视网膜血管生成。
