title: Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization.
abstract: Pathologic ocular neovascularization commonly causes blindness. It is critical to identify the factors altered in pathologically proliferating versus normally quiescent vessels to develop effective targeted therapeutics. MicroRNAs regulate both physiological and pathological angiogenesis through modulating expression of gene targets at the posttranscriptional level. However, it is not completely understood if specific microRNAs are altered in pathologic ocular blood vessels, influencing vascular eye diseases. Here we investigated the potential role of a specific microRNA, miR-150, in regulating ocular neovascularization. We found that miR-150 was highly expressed in normal quiescent retinal blood vessels and significantly suppressed in pathologic neovessels in a mouse model of oxygen-induced proliferative retinopathy. MiR-150 substantially decreased endothelial cell function including cell proliferation, migration, and tubular formation and specifically suppressed the expression of multiple angiogenic regulators, CXCR4, DLL4, and FZD4, in endothelial cells. Intravitreal injection of miR-150 mimic significantly decreased pathologic retinal neovascularization in vivo in both wild-type and miR-150 knockout mice. Loss of miR-150 significantly promoted angiogenesis in aortic rings and choroidal explants ex vivo and laser-induced choroidal neovascularization in vivo. In conclusion, miR-150 is specifically enriched in quiescent normal vessels and functions as an endothelium-specific endogenous inhibitor of pathologic ocular neovascularization.
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Chi-Hsiu
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Ye
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115; Department of Ophthalmology, Sichuan Provincial People's Hospital and Sichuan Academy of Medical Science, Chengdu, Sichuan 610027, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Tian
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Lucy P
authors.initials: LP
authors.lastname: Evans
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Peyton C
authors.initials: PC
authors.lastname: Morss
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Fredrick
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Saba
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115; jing.chen@childrens.harvard.edu.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000235:genetics* / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D058449:Intravitreal Injections; D061346:Laser Capture Microdissection; D008156:Luciferases; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D008969:Molecular Sequence Data; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D015861:Retinal Neovascularization / Q000235:genetics* / Q000378:metabolism; D012171:Retinal Vessels / Q000166:cytology* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; C514936:CXCR4 protein, mouse; D002135:Calcium-Binding Proteins; C519665:DLL4 protein, mouse; D051157:Frizzled Receptors; C498581:Fzd4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D035683:MicroRNAs; C529101:Mirn150 microRNA, mouse; D019718:Receptors, CXCR4; D008156:Luciferases
keywords: endothelial cells; miR-150; microRNA; neovascularization; retinopathy