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.
Highlights
Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries, affecting more than 50 million people over the age of 60 worldwide [1,2]
The expression of miR-126 in mice eyes was measured by qPCR (RPE/choroid mix n = 12). miR-126 was significantly downregulated (p < 0.05) in the choroidal neovascularization (CNV) eyes compared with the untreated eyes (Figure 1)
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Summary
Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries, affecting more than 50 million people over the age of 60 worldwide [1,2]. The “wet” form of AMD is associated with severe vision loss involving the progressive growth of abnormal, permeable blood vessels from the choroid into the subretinal space, known as Characterized by choroidal neovascularization (CNV) [3,4]. Organisms require an appropriate balance of stability and reversibility in gene transcription and translation to maintain cell identity or to enable responses to stimuli. This process is tightly regulated by proteinous and nonproteinous complexes such that, even slight dysregulation of this network results in the occurrence of several human diseases [7]. Anti-VEGF treatment has been used widely in treating neovascular AMD.
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