title: miR-126 Regulation of Angiogenesis in Age-Related Macular Degeneration in CNV Mouse Model.
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.
authors.affiliation: Eye Hospital, First Affiliated Hospital, Harbin Medical University, Harbin 150001, China. wangleiPHD@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Therapeutics, Drug Delivery Unit, Centre for Eye Research Australia, University of Melbourne, East Melbourne VIC 3000, Australia. amylee1192@gmail.com.
authors.forename: Amy Yi Wei
authors.initials: AY
authors.lastname: Lee
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, East Melbourne VIC 3000, Australia. jonathanwigg@outlook.com.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Wigg
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, East Melbourne VIC 3000, Australia. hiteshp@163.com.
authors.forename: Hitesh
authors.initials: H
authors.lastname: Peshavariya
authors.affiliation: Eye Hospital, First Affiliated Hospital, Harbin Medical University, Harbin 150001, China. pingliu53@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Eye Hospital, First Affiliated Hospital, Harbin Medical University, Harbin 150001, China. hong.zhang@unimelb.edu.au.|Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, East Melbourne VIC 3000, Australia. hong.zhang@unimelb.edu.au.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002465:Cell Movement; D020256:Choroidal Neovascularization / Q000235:genetics; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D015861:Retinal Neovascularization / Q000235:genetics*; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: C545201:MIRN126 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A
keywords: age-related macular degeneration; choroidal neovascularization; human microvascular endothelial cell (HMEC); miR-126