Hsa_circ_0004776 regulates the retina neovascularization in progression of diabetic retinopathy via hsa-miR-382-5p/BDNF axis

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.

Keywords:

• diabetic retinopathy
• hsa_circ_0004776
• hsa-miR-382-5p
• retinal neovascularization
• rat model

Authors’ contributions

Lu Ye: Conceptualisation, Validation, Data curation. Yixiu Chen and Wendong Gu: Conceptualisation, Methodology, Data curation, Resources, Formal analysis. Jun Shao: Methodology, Data curation, Formal analysis, Supervision, Funding acquisition. Yu Xin: Project administration, Supervision, Funding acquisition, Writing-original draft.

Disclosure statement

The authors report there are no competing interests to declare.

Data availability statement

The data that support the findings of this study are available from the corresponding author, [YX], upon reasonable request.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China under Grant [number 81970819]; China Postdoctoral Science Foundation under Grant [number 2020M671541]; Youth Medical Talent Project of Jiangsu Province under Grant [number QNRC2016182]; and Top Talent Support Program for young and middle-aged people of Wuxi Health Committee under Grant [number BJ2020012].