Downregulation of miR-145-5p elevates retinal ganglion cell survival to delay diabetic retinopathy progress by targeting FGF5

• Published in: Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2019-09, Vol.83 (9), p.1655-1662
• Main Authors: Zhang, Jingjing, Cui, Changlei, Xu, Haiyang
• Format: Article
• Language: English
• Subjects: Apoptosis; Cell Line; Cell Survival; Cytokines - metabolism; Diabetic retinopathy; Diabetic Retinopathy - metabolism; Diabetic Retinopathy - pathology; Down-Regulation; FGF5; Fibroblast Growth Factor 5 - genetics; Fibroblast Growth Factor 5 - metabolism; Glucose - metabolism; Humans; Inflammation Mediators - metabolism; MicroRNAs - metabolism; miR-145-5p; retinal ganglion cells; Retinal Ganglion Cells - cytology; Retinal Ganglion Cells - metabolism
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1080/09168451.2019.1630251

Diabetic retinopathy (DR) is a leading cause of new-onset blindness. Recent studies showed that protecting retinal ganglion cells (RGCs) from high glucose-induced injury is a promising strategy for delaying DR. This study is to investigate the role of miR-145-5p in high glucose-induced RGC injury. Here, RGCs were randomly divided into low glucose and high glucose groups. PCR assay showed miR-145-5p was significantly upregulated in high glucose group. Transfection of miR-145-5p inhibitor decreased pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) levels, elevated cell viability and proliferation, as well as suppressed cell apoptosis by ELISA, MTT, EdU proliferation, colony formation and flow cytometry assays, respectively. Moreover, dual-luciferase reporter assay confirmed FGF5 as a target gene of miR-145-5p. FGF5 knockdown could partially reverse the protective effects of miR-145-5p on RGC-5 cells. In conclusion, our results demonstrated that inhibition of miR-145-5p might be a neuroprotective target for diabetes mellitus-related DR. Abbreviations: DR: diabetic retinopathy; RGCs: retinal ganglion cells; miR-145-5p: microRNA-145-5p; TNF-α: tumor necrosis factor-α; IL-6: interleukin-6; FGF: fibroblast growth factor; ATCC: American Type Culture Collection; WT: wild type; MUT: mutant type Inhibition of miR-145-5p could protect retinal ganglion cells against high glucose at least in part through up-regulating FGF5 expression.