title: CD34 Promotes Pathological Epi-Retinal Neovascularization in a Mouse Model of Oxygen-Induced Retinopathy.
abstract: The sialomucins CD34 and podocalyxin (PODXL) are anti-adhesive molecules expressed at the luminal membrane of endothelial cells of small blood vessels and facilitate vascular lumen formation in the developing mouse aorta. CD34 transcript and protein levels are increased during human angiogenesis, its expression is particularly enriched on endothelial tip cell filopodia and CD34 is a marker for tip cells in vitro. Here, we investigated whether CD34 merely marks endothelial tip cells or has a functional role in tip cells and angiogenesis. We assessed that silencing CD34 in human microvascular endothelial cells has little effect on endothelial cell migration or invasion, but has a significant effect on vascular-endothelial growth factor-induced angiogenic sprouting activity in vitro. In vivo, the absence of CD34 reduced the density of filopodia on retinal endothelial tip cells in neonatal mice, but did not influence the overall architecture of the retinal vascular network. In oxygen-induced retinopathy, Cd34-/- mice showed normal intra-retinal regenerative angiogenesis but the number of pathological epi-retinal neovascular tufts were reduced. We conclude that CD34 is not essential for developmental vascularization in the retina, but its expression promotes the formation of pathological, invasive vessels during neovascularization.
authors.affiliation: Ocular Angiogenesis Group, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Ophthalmology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Cell Biology and Histology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Siemerink
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.|The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Michael R
authors.identifier: http://orcid.org/0000-0002-7925-6070
authors.initials: MR
authors.lastname: Hughes
authors.affiliation: Ocular Angiogenesis Group, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Ophthalmology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Cell Biology and Histology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Marchien G
authors.initials: MG
authors.lastname: Dallinga
authors.affiliation: Ocular Angiogenesis Group, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Ophthalmology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Cell Biology and Histology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Tomek
authors.initials: T
authors.lastname: Gora
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.|Department of Experimental Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Cait
authors.affiliation: Ocular Angiogenesis Group, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Ophthalmology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Cell Biology and Histology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Ilse M C
authors.initials: IM
authors.lastname: Vogels
authors.affiliation: Ocular Angiogenesis Group, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Ophthalmology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Cell Biology and Histology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Bahar
authors.initials: B
authors.lastname: Yetin-Arik
authors.affiliation: Ocular Angiogenesis Group, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Ophthalmology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Cell Biology and Histology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Cornelis J F
authors.initials: CJ
authors.lastname: Van Noorden
authors.affiliation: Ocular Angiogenesis Group, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Ophthalmology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Cell Biology and Histology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Klaassen
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.|The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.|Department of Experimental Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McNagny
authors.affiliation: Ocular Angiogenesis Group, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Ophthalmology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.|Department of Cell Biology and Histology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Reinier O
authors.initials: RO
authors.lastname: Schlingemann
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010100:Oxygen / Q000633:toxicity; D012171:Retinal Vessels / Q000378:metabolism; D012178:Retinopathy of Prematurity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D012795:Sialoglycoproteins; C001643:podocalyxin; D010100:Oxygen