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miR-365 promotes diabetic retinopathy through inhibiting Timp3 and increasing oxidative stress
Journal article   Peer reviewed

miR-365 promotes diabetic retinopathy through inhibiting Timp3 and increasing oxidative stress

Juan Wang, Jieping Zhang, Xin Chen, Yiting Yang, Fang Wang, Weiye Li, Maihemuti Awuti, Yaping Sun, Chunpin Lian, Zongyi Li, …
Experimental eye research, v 168, pp 89-99
Mar 2018
DOI: https://doi.org/10.1016/j.exer.2017.11.006
PMID: 29196060
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Diabetic retinopathy miR-365 Müller cells Oxidative stress Timp3
miRs play critical roles in oxidative stress-related retinopathy pathogenesis. miR-365 was identified in a previously constructed library from glyoxal-treated rat Müller cell. This report explores epigenetic alterations in Müller cells under oxidative stress to develop a novel therapeutic strategy. To examine the miR-365 expression pattern, in situ hybridization and quantitative RT-PCR were performed. Bioinformatical analysis and dual luciferase report assay were applied to identify and confirm target genes. Streptozotocin (STZ)-treated rats were used as the diabetic retinopathy (DR) model. Lentivirus-mediated anti-miR-365 was delivered subretinally and intravitreally into the rats’ eyes. The functional and structural changes were evaluated by electroretinogram (ERG), histologically, and through examination of expression levels of metallopeptidase inhibitor 3 (Timp3), glial fibrillary acidic protein (Gfap), recoverin (Rcvrn) and vascular endothelia growth factor A (Vegfa). Oxidative stress factors and pro-inflammatory cytokines were analyzed. miR-365 expression was confirmed in the glyoxal-treated rat Müller cell line (glyoxal-treated rMC-1). In the retina, miR-365 mainly localized in the inner nuclear layer (INL). The increased miR-365 participated in Müller cell gliosis through oxidative stress aggravation, as observed in glyoxal-treated rMC-1 and DR rats before 6 weeks. Timp3 was a target and negatively regulated by miR-365. When miR-365 was inhibited, Timp3 expression was upregulated, Müller cell gliosis was alleviated, and retinal oxidative stress was attenuated. Visual function was also partially rescued as detected by ERG. miR-365 was found to be highly expressed in the retina and the abnormality of miR-365/Timp3 pathway is closely related to the pathology, like Müller gliosis, and the visual injury in DR. The mechanism might be through oxidative stress, and miR-365/Timp3 could be a potential therapeutic target for treating DR. •miR-365 in rat retina is mainly expressed in INL, photoreceptor layer, and RPE layer.•Timp3 is the direct target of and negatively regulated by miR-365.•The increased miR-365 in Müller cells is involved in DR through miR-365/Timp3 pathway and oxidative stress mechanism.

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Web of Science research areas
Ophthalmology
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