title: The absence of angiopoietin-2 leads to abnormal vascular maturation and persistent proliferative retinopathy.
abstract: Angiopoietin-2 (Ang-2) antagonises the maturing effect of angiopoietin-1 (Ang-1) on blood vessels, and cooperates with VEGF to induce neovascularisation. In knockout mice, Ang-2 displayed a specific role in postnatal angiogenic remodelling. Here, we demonstrate that mice deficient in Ang-2 fail to form a proper spatial retinal vascular network. The retinal vasculature was characterised by reduced large vessel numbers and defects forming the superficial periphery mostly on the arteriolar site, and the secondary and tertiary deep capillary network. Hypoxia in the retinal periphery induced a four-fold VEGF upregulation and active endothelial proliferation for up to 60 days. Concomitantly, retinal digest preparations showed increased arteriolar (+33%) and capillary diameters (+90%), and fluorescein angiograms revealed leakiness of neovascular front. At one year of age, persistent preretinal vessels were non-leaky in accordance with a relative increase in the ratio of Ang-1 to VEGF. Taken together, the data suggest that Ang-2 has an important function in the spatial configuration of the three-dimensional retinal vasculature. Secondarily, prolonged VEGF activity results in a model of persistent proliferative retinopathy.
authors: 5th Medical Clinic, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors: Yuxi
authors: Y
authors: Feng
authors: Franziska
authors: F
authors: Vom Hagen
authors: Yumei
authors: Y
authors: Wang
authors: Susanne
authors: S
authors: Beck
authors: Kay
authors: K
authors: Schreiter
authors: Frederick
authors: F
authors: Pfister
authors: Sigrid
authors: S
authors: Hoffmann
authors: Patrick
authors: P
authors: Wagner
authors: Mathias
authors: M
authors: Seeliger
authors: Grietje
authors: G
authors: Molema
authors: Urban
authors: U
authors: Deutsch
authors: Hans-Peter
authors: HP
authors: Hammes
mesh_terms: D000367:Age Factors; D000375:Aging / Q000473:pathology; D000792:Angiography; D042702:Angiopoietin-2 / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D004396:Coloring Agents; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D007208:Indocyanine Green; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007763:Lac Operon; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation; D015861:Retinal Neovascularization / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D012171:Retinal Vessels / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042702:Angiopoietin-2; D004396:Coloring Agents; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D007208:Indocyanine Green