Slit-miR-218-Robo axis regulates retinal neovascularization

Kong,Yichun; Sun,Bei; Han,Quanhong; Han,Shuang; Wang,Yuchuan; Chen,Ying

doi:10.3892/ijmm.2016.2511

Slit-miR-218-Robo axis regulates retinal neovascularization

Authors:
- Yichun Kong
- Bei Sun
- Quanhong Han
- Shuang Han
- Yuchuan Wang
- Ying Chen
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Affiliations: Tianjin Eye Hospital, Heping, Tianjin 300020, P.R. China, Key Laboratory of Hormones and Development, Ministry of Health, Heping, Tianjin 300070, P.R. China
Published online on: February 29, 2016 https://doi.org/10.3892/ijmm.2016.2511
Pages: 1139-1145

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Abstract

miR-218 is an important intronic microRNA (miRNA or miR) which is known to regulate angiogenesis in tumors. The present study aimed to investigate the effects of miR-218, as well as its host genes, Slit2 and Slit3, on oxygen-induced retinal neovascularization (RNV) and to explore the associated mechanisms of action. For this purpose, a mouse model of oxygen-induced retinopathy (OIR) was established. The expression levels of miR-218-1 and miR-218-2, as well as those of their host genes, Slit2 and Slit3, were determined by RT-qPCR. Fluorescein angiography was performed on the retinas of the mice with OIR, and RNV was quantified by H&E staining in order to evaluate the effect of pCDH-CMV-miR-218 intravitreal injection on RNV in the mouse model of OIR. Roundabout, axon guidance receptor, homolog 1 (Robo1) expression was detected in mouse retinal vascular endothelial cells expressing high or low levels of miR-218 and in retinal tissues from mice with OIR by western blot analysis. Cell migration was evaluated by a scratch wound assay. We noted that in the mice with OIR, the expression level of miR-218 was significantly downregulated. We also noted that Robo1 expression was suppressed by miR-218. Furthermore, in the mice with OIR, the expression level of miR-218 was significantly downregulated, and that of miR-218-1 and its host gene, Slit2, was concomitantly downregulated as well. The restoration of miR-218 inhibited retinal angiogenesis by targeting Robo1. Taken together, our findings suggest that the Slit2-miR-218-Robo1 axis contributes to the inhibition of retinal angiogenesis and that miR-218 may be a new therapeutic target for preventing RNV.

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