Abstract
P 089
Aniopoietin-2 deficient mouse is a spontaneous mouse model for hypoxia-induced neovascularization
Yuxi Feng1, Franziska vom Hagen1, Yumei Wang1, Susanne Beck2, Mathias Seeliger2, Hans-Peter Hammes1, Urban Deutsch3
1University of Heidelberg, Faculty of Clinical Medicine Mannheim, 5th Medical Clinic, Mannheim, Germany, 2University of Tuebingen, Retinal Electrodiagnostics Research Group, Tübingen, Germany, 3University of Berne, Theodor-Kocher-Institute, Bern, Switzerland
Objective
Angiopoietin-2 (Ang-2) is a crucial player in physiological as well as in pathological angiogenesis. Ang-2 deficient mouse displayed a defective retinal angiogenic remodelling in the first month of life. However, its precise prolonged outcome is unknown. We investigated in this study the detailed development of retinal vessels in Ang-2 deficient mouse up to one year.
Methods
Immunofluorescence staining with lectin was used to visualize retinal vessels. Hypoxia and leakiness were assessed by Hypoxyprobe and scanning laser ophthalmoscope (SLO), respectively. Expression of VEGF was detected by Taqman real time PCR.
Results
Ang-2 deficiency resulted in malformation of retinal vascular network with reduced large vessel numbers and defects forming the superficial periphery mostly on the arteriolar site, and the secondary and tertiary deep capillary network. Pre-retinal neovascularizations were evidenced up to one year beyond the onset of neovascularization at postnatal day 10 (p10). Hypoxia was strongly detected in the avascular retinal periphery at p10. SLO revealed leakiness of pre-retinal neovascular fronds at early age, but not at one year. Quantitative PCR showed highly upregulated VEGF only at early age in the Ang-2 deficient retina.
Conclusions
The data suggest that Ang-2 has an important function in the spatial configuration of the three-dimensional retinal vasculature. Delayed formation of retinal vessels in Ang-2 deficient mouse leads to hypoxia in the retina, upregulation of VEGF and subsequent hypoxia-induced neovascularization. Aniopoietin-2 deficient mouse is a spontaneous mouse model for hypoxia-induced neovascularization.
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