Open AccessCD34 Promotes Pathological Epi-Retinal Neovascularization in a Mouse Model of Oxygen-Induced Retinopathy
Author(s) -
Martin J. Siemerink,
Michael R. Hughes,
Marchien G. Dallinga,
Tomek Gora,
Jessica Cait,
I. M. C. Vogels,
Bahar Yetin-Arik,
C. J. F. Van Noorden,
Ingeborg Klaassen,
Kelly M. McNagny,
Reinier O. Schlingemann
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0157902
Subject(s) - angiogenesis , neovascularization , cd34 , microbiology and biotechnology , filopodia , biology , endothelial stem cell , vasculogenesis , retinal , vascular endothelial growth factor , retina , podocalyxin , pathology , progenitor cell , cancer research , stem cell , medicine , in vitro , endocrinology , neuroscience , actin , biochemistry , vegf receptors , proteinuria , podocyte , kidney
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.