Journal
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 57, Issue 3, Pages 1398-1407Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.15-17417
Keywords
microRNA-184; corneal neovascularization; VEGF; Wnt/beta-catenin
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Funding
- Natural Science Foundation of China, Beijing, China [81400379, 81170818]
- National High Technology Research and Development Program of China, Beijing, China [2012AA020507]
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PURPOSE. Although microRNA-184 (miR-184) is abundantly expressed in the corneas, the role of miR-184 in corneal neovascularization remains unknown. Here we investigated the association between miR-184 expression and corneal neovascularization. METHODS. Quantitative real-time PCR assay was conducted to detect the expression of miR-184 and its potential target genes in the corneal epithelium of rats with corneal suture-induced neovascularization. MicroRNA-184 was also applied topically to the suture rats. Mimic and inhibitor of miR-184 were transfected into the cultured human umbilical vein endothelial cells (HUVECs), human corneal epithelial (HCE) cells, and simian choroidal endothelial cells (RF/6A). The following experiments were performed to evaluate the effects of miR-184 in these transfected cells: cell proliferation by cell viability assay, cell migration by a scratch wound test, VEGF-induced tube formation, and VEGF and beta-catenin levels by Western blot analysis. RESULTS. The expression of miR-184 was significantly reduced, whereas the gene expression of frizzled-4, a receptor of the Wnt pathway, was up-regulated in the corneal epithelium of corneal suture rats. The corneal neovascularization induced by suture was ameliorated by topical administration of miR-184. In the cells transfected with mimic and inhibitor of miR-184, miR-184 significantly suppressed the cell proliferation and cell migration of HUVECs, miR-184 down-regulated VEGF, and beta-catenin expression in HUVECs and HCE cells. Furthermore, miR-184 inhibited the tube formation of RF/6A cells. CONCLUSIONS. Down-regulation of miR-184 is associated with up-regulation of VEGF and Wnt/beta-catenin expression as well as corneal neovascularization, indicating that miR-184 negatively regulates corneal neovascularization.
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