Significant role of microRNA-219-5p in diabetic retinopathy and its mechanism of action

Abstract

Diabetic retinopathy (DR) is the leading cause of blindness and visual impairment. The role of microRNA (miRNA) in DR remains largely unknown. The present study aimed to investigate the role of miR-219-5p in the progression of DR. Human retinal pigment epithelial (RPE) cells were treated with a high concentration of glucose (50 mM D-glucose) for 24 h and the miR-219-5p level was detected using reverse transcription-quantitative polymerase chain reaction. The results revealed that miR-219-5p was significantly upregulated by high glucose (HG) treatment. To explore the role and mechanism of miR-219-5p in DR progression, miR-219-5p was downregulated in ARPE-19 cells. An MTT assay and flow cytometry were used to determine the level of viability and apoptosis of ARPE-19 cells, respectively. MicroRNA.org was used to predict the targets of miR-219-5p and the prediction was investigated using a dual-luciferase reporter assay. In addition, the level of associated proteins were measured using western blot analysis. It was observed that liver receptor homolog-1 (LRH-1) was a direct target of miR-219-5p. LRH-1 was significantly downregulated in ARPE-19 cells following HG treatment and negatively regulated by miR-219-5p in ARPE-19 cells. MiR-219-5p inhibitor significantly prevented ARPE-19 cell apoptosis induced by HG treatment and cell viability was markedly promoted. The results also suggested that the LRH-1/Wnt/?-Catenin signaling pathway was activated by miR-219-5p inhibition. In addition, it was revealed that LRH-1 inhibition eliminated the effects of miR-219-5p inhibitor on ARPE-19 cells. In conclusion, the results indicated that miR-219-5p was involved in the progression of DR through regulating human RPE cell apoptosis by modulation of the LRH-1/Wnt/?-Catenin signaling pathway.