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MicroRNA-410 reduces the expression of vascular endothelial growth factor and inhibits oxygen-induced retinal neovascularization.

ABSTRACT: Retinal neovascularization (RNV) is an eye disease that can cause retinal detachment and even lead to blindness. RNV mainly occurs in the elderly population. The pathogenesis of RNV has been previously reported to be highly related to the expression of vascular endothelial growth factor A (VEGFA), basic fibroblast growth factor (bFGF) and other angiogenic factors. It has also been reported that VEGFA and other factors associated with RNV could be regulated by certain microRNAs (miRNA), a group of small non-coding RNAs which are able to regulate the expression of many genes in vivo. Here, we demonstrate that the miRNA miR-410 is highly expressed in mice within two weeks after birth. miR-410 could suppress VEGFA expression through interaction with the 3'UTR of the VEGFA messenger RNA. Overexpressing a miR-410 mimic effectively suppresses VEGFA expression in various cell lines. Further experiments on oxygen-induced retinopathy (OIR) in mice revealed that eye drops containing large amounts of miR-410 efficiently downregulate VEGFA expression, prevent retinal angiogenesis and effectively treat RNV. These results not only show the underlying mechanism of how miR-410 targets VEGFA but also provide a potential treatment strategy for RNV that might be used in the near future.

SUBMITTER: Chen N

PROVIDER: S-EPMC4002426 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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MicroRNA-410 reduces the expression of vascular endothelial growth factor and inhibits oxygen-induced retinal neovascularization.

Chen Na N Wang Jiaqi J Hu Yijun Y Cui Bei B Li Wenjie W Xu Guixia G Liu Lin L Liu Shanrong S

PloS one 20140428 4

Retinal neovascularization (RNV) is an eye disease that can cause retinal detachment and even lead to blindness. RNV mainly occurs in the elderly population. The pathogenesis of RNV has been previously reported to be highly related to the expression of vascular endothelial growth factor A (VEGFA), basic fibroblast growth factor (bFGF) and other angiogenic factors. It has also been reported that VEGFA and other factors associated with RNV could be regulated by certain microRNAs (miRNA), a group o ...[more]

PMID: 24777200

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Project description:The present study aimed to investigate the significant role of ?-elemene in mouse models of oxygen-induced retinopathy (OIR). C57BL/6J neonatal mice were used to establish OIR models. They were divided into four groups: Normoxia, OIR, OIR control and OIR?treated. Mice in the OIR group were exposed to 75±5% oxygen for 5 days and returned to a normal oxygen environment on postnatal day 12 (P12). The OIR treated group was intravitreally injected with 1 µl ??elemene on P12 and subsequently returned to a normal oxygen environment for 5 days (P12?P17). Retinas were obtained on P17. Retinal neovascularization (RNV) was detected using adenosine diphosphatase staining and analyzed by counting the nuclei of neovascular endothelial cells. Vascular endothelial growth factor (VEGF) expression was determined by reverse transcription?quantitative polymerase chain reaction, immunohistochemistry and western blot analysis. MicroRNA (miRNA/miR) microarrays were used to screen out differentially expressed miRNAs between the OIR and ??elemene?treated groups. Binding the 3'?untranslated region (UTR) of VEGF and miR?27a was confirmed using luciferase assays. It was found that high oxygen concentrations accelerated RNV and increased the number of preretinal neovascular cells; ??elemene treatment reduced these effects. VEGF mRNA and protein expression was higher in the OIR and OIR control groups, compared with the normoxia and OIR?treated groups. Further, it was shown that miR?22, miR?181a?1, miR?335?5p, miR?669n, miR?190b, miR?27a and miR?93 were upregulated in the OIR?treated group, and downregulated in the OIR group. The prediction websites TargetScan and miRanda revealed that VEGF contained a potential miR?27a binding site in its 3'?untranslated region (UTR). Luciferase assays demonstrated that miR?27a directly bound to the 3'?UTR of VEGF. In vitro experiments demonstrated that miR?27a inhibited VEGF expression. In addition, ??elemene treatment upregulate miR?27a expression in vivo and in vitro. When miR?27a expression was depleted by miR?27a inhibitor, the protective effect of ??elemene on RNV was eliminated. The present study demonstrated that ??elemene reduced RNV in mouse OIR models via miR?27a upregulation, leading to reduced VEGF expression. This finding may contribute to the development of novel therapeutic strategies for human retinopathy.

Dataset Information

MicroRNA-410 reduces the expression of vascular endothelial growth factor and inhibits oxygen-induced retinal neovascularization.

Publications

MicroRNA-410 reduces the expression of vascular endothelial growth factor and inhibits oxygen-induced retinal neovascularization.

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