title: miRNA involvement in angiogenesis in age-related macular degeneration.
abstract: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Late-stage AMD is characterized by choroidal neovascularization (CNV). miR-93 appears to play a role in regulating vascular endothelial growth factor-A (VEGF-A), a known factor involved in neovascularization. Understanding its biological significance might enable development of therapeutic interventions for diseases like AMD. We aimed to determine the role of miR-93 in AMD using a laser-induced CNV mouse model. CNV was induced by laser photocoagulation in C57BL/6 mice. The CNV mice were transfected with scrambled miR or miR-93 mimic. The treatment effect was assessed by fundus photography and fluorescein angiography and confirmed by choroidal flatmount. The expression of miR-93 and VEGF-A in ocular tissues was analysed by quantitative polymerase chain reaction (qPCR) and Western blot. The overexpression effects of miR-93 were also proved on human microvascular endothelial cells (HMECs). Significantly decreased expression of miR-93 was observed by qPCR analysis in CNV mice compared to untreated mice (p < 0.05). VEGF-A messenger RNA (mRNA) and protein expression were upregulated with CNV; these changes were ameliorated by restoration of miR-93 (p < 0.05). CNV was reduced after miR-93 transfection. Transfection of miR-93 reduced the proliferation of HMECs (p < 0.01), but no significant changes were observed in 2D capillary-like tube formation (p > 0.05) and migration (p > 0.05) compared with that in the untreated cells. miR-93 has been shown to be a negative modulator of angiogenesis in the eye. All together, these results highlight the therapeutic potential of miR-93 and suggest that it may contribute as a putative therapeutic target for AMD in humans.
authors.affiliation: Eye Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, VIC, Australia.|Drug Delivery Unit, Centre for Eye Research Australia, Melbourne, VIC, Australia.
authors.forename: Amy Yi Wei
authors.initials: AY
authors.lastname: Lee
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, 32 Gisborne Street, East Melbourne, VIC, 3002, Australia.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Wigg
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, 32 Gisborne Street, East Melbourne, VIC, 3002, Australia.
authors.forename: Hitesh
authors.initials: H
authors.lastname: Peshavariya
authors.affiliation: Eye Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, China. pingliu53@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Eye Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, China. hong.zhang@unimelb.edu.au.|Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, 32 Gisborne Street, East Melbourne, VIC, 3002, Australia. hong.zhang@unimelb.edu.au.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D020256:Choroidal Neovascularization / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005451:Fluorescein Angiography; D005786:Gene Expression Regulation; D006801:Humans; D007834:Lasers; D008028:Light Coagulation / Q000009:adverse effects; D008268:Macular Degeneration / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D018716:Molecular Mimicry; D009843:Oligoribonucleotides / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C551470:Mirn93 microRNA, mouse; D009843:Oligoribonucleotides; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse
keywords: Age-related macular degeneration; Choroidal neovascularization; HMEC; VEGF-A; miR-93