The absence of angiopoietin-2 leads to abnormal vascular maturation and persistent proliferative retinopathy.
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.
Feng
Yuxi
Y
5th Medical Clinic, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Vom Hagen
Franziska
F
Wang
Yumei
Y
Beck
Susanne
S
Schreiter
Kay
K
Pfister
Frederick
F
Hoffmann
Sigrid
S
Wagner
Patrick
P
Seeliger
Mathias
M
Molema
Grietje
G
Deutsch
Urban
U
Hammes
Hans-Peter
HP
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
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