Impaired pericyte recruitment and abnormal retinal angiogenesis as a result of angiopoietin-2 overexpression.
Angiopoietin-2 (Ang2) is among the relevant growth factors induced by hypoxia and plays an important role in the initiation of retinal neovascularizations. Ang2 is also involved in incipient diabetic retinopathy, as it may cause pericyte loss. To investigate the impact of Ang2 on developmental and hypoxia-induced angiogenesis, we used a transgenic mouse line overexpressing human Ang2 in the mouse retina. Transgenic mice displayed a reduced coverage of capillaries with pericytes (-14%; p < 0.01) and a 46% increase of vascular density of the capillary network at postnatal day 10 compared to wild type mice. In the model of oxygen-induced retinopathy (OIR), Ang2 overexpression resulted in enhanced preretinal (+103%) and intraretinal neovascularization (+29%). Newly formed intraretinal vessels in OIR were also pericyte-deficient (-26%; p < 0.01). The total expression of Ang2 in transgenic mice was seven-fold, compared with wild type controls. Ang2 modulated expression of genes encoding VEGF (+65%) and Ang1 (+79%) in transgenic animals. These data suggest that Ang2 is involved in pericyte recruitment, and modulates intraretinal, and preretinal vessel formation in the eye under physiological and pathological conditions.
Feng
Yuxi
Y
5th Medical Clinic, Faculty of Clinical Medicine, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.
vom Hagen
Franziska
F
Pfister
Frederick
F
Djokic
Snezana
S
Hoffmann
Sigrid
S
Back
Walter
W
Wagner
Patrick
P
Lin
Jihong
J
Deutsch
Urban
U
Hammes
Hans-Peter
HP
D042683:Angiopoietin-1 / Q000235:genetics; D042702:Angiopoietin-2 / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D003930:Diabetic Retinopathy; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic; D020286:Pericytes / Q000473:pathology*; D015861:Retinal Neovascularization / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042461:Vascular Endothelial Growth Factor A