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Yusuke Takahashi, Qian Chen, Raju V S Rajala, Jian-Xing (Jay) Ma; FUNCTIONAL ROLE OF MICRORNA-184 IN DIABETIC RETINOPATHY.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5169. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
MicroRNAs (miRNAs) are known to participate in post transcriptional regulation of gene expression and are involved in multiple pathogenic processes. It was recently reported that the some miRNAs change their expression during the development and progression of various diseases including diabetes. The purposes of this study were to identify differential expression of miRNAs in the retinas of oxygen-induced retinopathy (OIR) mice, a model of proliferative retinopathy, and to elucidate the potential role of miRNAs implicated in the pathophysiology of diabetic retinopathy (DR).
MiRNA expression changes in the mouse retinas of OIR were identified by quantitative reverse transcription-PCR (qRT-PCR). The potential candidate genes of identified miRNAs were predicted by bioinformatics analysis and validated by luciferase-based assay. The mRNA and/or protein levels of identified downstream targets of miRNA were examined by qRT-PCR and Western blot analysis. Furthermore, we evaluated the in vivo functional role of miRNA in the retina of OIR mice
The qRT-PCR showed that miR-184 was significantly down-regulated in the retina of OIR mice. Bioinformatics analysis predicted that some components of Wnt signaling may be regulated by miR-184. Thus, we identified that Wnt signaling activity was significantly down-regulated by the transfection of precursor miR-184 (mimic), whereas up-regulated by the transfection of anti-sense miR-184 (inhibitor). Furthermore, we identified that frizzled-7 (Fzd7) is a downstream target gene regulated by miR-184 using dual luciferase assay. Delivery of miR-184 mimic showed significant inhibition of Wnt signaling activity as well as down-regulation of Fzd7, a downstream target of miR-184, and Vegf-a, a downstream target of Wnt signaling, in the retina of OIR mice
It has been shown that aberrant activation of Wnt signaling in the diabetic retina may cause pathogenesis of diabetic retinopathy. The present study suggests that down-regulation of miR-184 in the retina with ischemia-induced retinopathy may lead to activation of Wnt signaling, which plays an important role in the pathogenesis and progression of DR. Our studies also suggest that over-expression of miR-184 in the retina offers a therapeutic benefit to prevent inflammatory responses and/or neovascularization in DR.
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