miR-126 Regulation of Angiogenesis in Age-Related Macular Degeneration in CNV Mouse Model

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Wang, L; Lee, AYW; Wigg, JP; Peshavariya, H; Liu, P; Zhang, HDate
2016-06-01Source Title
International Journal of Molecular SciencesPublisher
MDPIAffiliation
Centre for Eye Research Australia (CERA)Metadata
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Wang, L., Lee, A. Y. W., Wigg, J. P., Peshavariya, H., Liu, P. & Zhang, H. (2016). miR-126 Regulation of Angiogenesis in Age-Related Macular Degeneration in CNV Mouse Model. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 17 (6), https://doi.org/10.3390/ijms17060895.Access Status
Open AccessAbstract
miR-126 has recently been implicated in modulating angiogenic factors in vascular development. Understandings its biological significance might enable development of therapeutic interventions for diseases like age-related macular degeneration (AMD). We aimed to determine the role of miR-126 in AMD using a laser-induced choroidal neovascularization (CNV) mouse model. CNV was induced by laser photocoagulation in C57BL/6 mice. The CNV mice were transfected with scrambled miR or miR-126 mimic. The expression of miR-126, vascular endothelial growth factor-A (VEGF-A), Kinase insert domain receptor (KDR) and Sprouty-related EVH1 domain-containing protein 1 (SPRED-1) in ocular tissues were analyzed by qPCR and Western blot. The overexpression effects of miR-126 were also proven on human microvascular endothelial cells (HMECs). miR-126 showed a significant decrease in CNV mice (p < 0.05). Both mRNA and protein levels of VEGF-A, KDR and SPRED-1 were upregulated with CNV; these changes were ameliorated by restoration of miR-126 (p < 0.05). CNV was reduced after miR-126 transfection. Transfection of miR-126 reduced the HMECs 2D-capillary-like tube formation (p < 0.01) and migration (p < 0.01). miR-126 has been shown to be a negative modulator of angiogenesis in the eye. All together these results high lights the therapeutic potential of miR-126 suggests that it may contribute as a putative therapeutic target for AMD in humans.
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