A single local injection of recombinant VEGF receptor 2 but not of Tie2 inhibits retinal neovascularization in the mouse.
OBJECTIVE
The purpose of this study was to develop pharmacological therapeutic alternatives for ischemia-induced proliferative retinopathy.


METHODS
C57BL/6J mice were placed in 76% oxygen on postnatal day 7 (P7) for 5 days. On P12 recombinant, chimeric vascular endothelial growth factor (sVEGF-R2) or sTie2 was injected intravitreally in one eye. The fellow eye received a control injection. On P17, retinal wholemounts were prepared after perfusion with fluorescein-dextran to quantify the retinopathy.


RESULTS
A single intravitreal injection of sVEGF-R2 reduced pathologic vascular changes significantly (p = 0.02). No significant effect was observed after intravitreal application of sTie2 (p = 0.07), although Ang-2 was upregulated in control animals without treatment as neovascularization developed and Ang-1 was constantly transcribed (ratio PCR).


CONCLUSIONS
sVEGF-R2 interferes with VEGF signaling via VEGF-R2 receptor. Thus, local application of soluble receptors for angiogenic factors is a possible therapy for proliferative retinopathy. Receptors with a wide range of ligands might prove more useful for local application than those binding few or antagonistic ligands.
Agostini
Hansjürgen
H
Department of Ophthalmology, University of Freiburg, Freiburg Germany. agostini@aug.ukl.uni-freiburg.de
Boden
Karl
K
Unsöld
Anke
A
Martin
Gottfried
G
Hansen
Lutz
L
Fiedler
Ulrike
U
Esser
Norbert
N
Marmé
Dieter
D
D042683:Angiopoietin-1 / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003911:Dextrans; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005451:Fluorescein Angiography; D005452:Fluoresceins; D007267:Injections; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000008:administration & dosage* / Q000378:metabolism; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D015861:Retinal Neovascularization / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000008:administration & dosage* / Q000378:metabolism; D014822:Vitreous Body
D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467628:Angpt1 protein, mouse; D003911:Dextrans; D005452:Fluoresceins; D012333:RNA, Messenger; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; C052526:fluorescein-dextran; D042787:Receptor, TIE-2; D040301:Vascular Endothelial Growth Factor Receptor-2; D010100:Oxygen