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Thromb Haemost 2009; 102(01): 120-130
DOI: 10.1160/TH08-09-0567
Endothelium and Vascular Development
Schattauer GmbH

The absence of angiopoietin-2 leads to abnormal vascular maturation and persistent proliferative retinopathy

Yuxi Feng
1   5th Medical Clinic, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
Franziska vom Hagen
1   5th Medical Clinic, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
Yumei Wang
1   5th Medical Clinic, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
Susanne Beck
2   Retinal Electrodiagnostics Research Group, University of Tuebingen, Tuebingen, Germany
,
Kay Schreiter
3   DeveloGen AG, Göttingen, Germany
,
Frederick Pfister
1   5th Medical Clinic, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
Sigrid Hoffmann
4   Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
Patrick Wagner
5   Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Germany
,
Mathias Seeliger
2   Retinal Electrodiagnostics Research Group, University of Tuebingen, Tuebingen, Germany
,
Grietje Molema
6   Laboratory for Endothelial Biomedicine and Vascular Drug Targeting Research, Medical Biology Section, Department Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
,
Urban Deutsch
7   Max-Planck-Institute for Vascular Biology, c/o Institute of Cell Biology, ZMBE, University of Muenster, and Theodor-Kocher-Institute, Berne, Switzerland
,
Hans-Peter Hammes
1   5th Medical Clinic, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
› Author AffiliationsFinancial support: This study was supported by grants from the Deutsche Forschungsgemeinschaft (SPP1069 for Y.F. and H.-P. H. and GRK 880 for H.-P. H., Y.F., F.v.H., Y.W. and F.P.) and the Deutsche Diabetes-Gesellschaft.
Further Information

Publication History

Received: 02 September 2008

Accepted after major revision: 13 April 2009

Publication Date:
24 November 2017 (online)

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Summary

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.

Keywords

Angiogenesis - VEGF - angiopoietin - proliferative retinopathy

 

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