Abstract：
The aim of this work was to identify the regulatory function of hsa_circ_0004776 in the progression of diabetic retinopathy (DR). The direct interactions between hsa_circ_0004776 and hsa-miR-382-5p and between hsa-miR-382-5p and BDNF, were confirmed via dual-luciferase reporter assays. Quantitative Real-Time PCR analysis indicated that hsa_circ_0004776 was highly expressed in aqueous humour samples of DR patients and human retinal microvascular epithelial cells (hRECs) under a high-glucose environment, whereas hsa-miR-382-5p showed the opposite trend. Overexpressed hsa_circ_0004776 significantly enhanced DNA synthesis, proliferation, migration, and tube formation in hRECs in hyperglycaemia, while hsa-miR-382-5p mimics reversed these changes. Additionally, in a streptozotocin-induced Sprague-Dawley rat model of DR, vitreous microinjection of rno-miR-382-5p agomir reversed the pathologic features in the progression of DR, including retinal vascular leakage, capillary decellularization, loss of pericytes, fibrosis, and gliosis. Our results indicated that under hyperglycaemic conditions, hsa_circ_0004776 influences the progression of DR via hsa-miR-382-5p and thus represents a potential therapeutic target.
摘要：
这项工作的目的是确定hsa_circ_0004776在糖尿病视网膜病变（DR）进展中的调节功能。hsa_circ_0004776与hsa-miR-382-5p以及hsa-miR-382-5p与BDNF之间的直接相互作用,通过双荧光素酶报告基因测定证实。实时定量PCR分析表明，在高糖环境下，DR患者的房水样本和人视网膜微血管上皮细胞（hRECs）中hsa_circ_0004776高表达，而hsa-miR-382-5p显示相反的趋势。过表达hsa_circ_0004776显著增强DNA合成,扩散,迁移,和高血糖的hRECs中的管形成，而hsa-miR-382-5p模拟逆转了这些变化。此外,在链脲佐菌素诱导的SD大鼠DR模型中，玻璃体显微注射rno-miR-382-5pagomir逆转了DR进展的病理特征，包括视网膜血管渗漏,毛细管去细胞化,周细胞的损失,纤维化，和神经胶质增生。我们的结果表明，在高血糖条件下，hsa_circ_0004776通过hsa-miR-382-5p影响DR的进展,因此代表潜在的治疗靶标。
