miR-126 Regulation of Angiogenesis in Age-Related Macular Degeneration in CNV Mouse ModelReportar como inadecuado




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1

Eye Hospital, First Affiliated Hospital, Harbin Medical University, Harbin 150001, China

2

Department of Pharmacology and Therapeutics, Drug Delivery Unit, Centre for Eye Research Australia, University of Melbourne, East Melbourne VIC 3000, Australia

3

Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, East Melbourne VIC 3000, Australia





*

Authors to whom correspondence should be addressed.



Academic Editor: Y-h. Taguchi

Abstract 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. View Full-Text

Keywords: miR-126; age-related macular degeneration; choroidal neovascularization; human microvascular endothelial cell HMEC miR-126; age-related macular degeneration; choroidal neovascularization; human microvascular endothelial cell HMEC





Autor: Lei Wang 1, Amy Yi Wei Lee 2, Jonathan P. Wigg 3, Hitesh Peshavariya 3, Ping Liu 1,* and Hong Zhang 1,3,*

Fuente: http://mdpi.com/



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