当前位置： SCI文献检索 > EXPERIMENTAL EYE RESEARCH期刊下所有文献 > miR-365 promotes diabetic retinopathy through inhibiting Timp3 and increasing oxidative stress.

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

Abstract：

: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.

journal_name

Exp Eye Res

journal_title

Experimental eye research

authors

Wang J,Zhang J,Chen X,Yang Y,Wang F,Li W,Awuti M,Sun Y,Lian C,Li Z,Wang M,Xu JY,Jin C,Tian H,Gao F,Zhang J,Sinha D,Lu L,Xu GT

doi

10.1016/j.exer.2017.11.006

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

89-99

eissn

0014-4835

issn

1096-0007

pii

S0014-4835(17)30505-5

journal_volume

168

pub_type

杂志文章

在线工具

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