Inhibition of corneal neovascularization by alpha(v)-integrin antagonists in the rat.
BACKGROUND
The proliferation of vascular endothelial cells and ultimately angiogenesis is inhibited by blocking integrin-mediated cell-matrix interaction. To asses the therapeutic potential of alpha(v)-integrin antagonists LM609 and cRGDfV in neovascularization of the anterior segment, their inhibitory effect on angiogenesis was studied in two rat models for corneal neovascularization.


METHODS
Corneal neovascularization was induced in Wistar rats (n=51) either by silver nitrate burns or intrastromal implantation of polymer pellets containing 400 ng of fibroblast growth factor (bFGF). Animals were treated with subcutaneous injections of a cyclic alpha(v)-integrin antagonist (cRGDfV, 15 mg/kg body wt) or saline twice daily. Additional animals received intrastromal implants containing 400 ng bFGF together with either Lm609 (mAb, anti-alpha(v)beta(3)) or control antibody. Four days later, the animals were killed and the percentage of the surface area covered with vessels determined using digital image analysis.


RESULTS
Systemic treatment with cRGDfV resulted in a significant reduction of corneal vessel growth in animals with bFGF-induced corneal vascularization. In corneas with silver nitrate burns, systemic cRGDfV treatment showed no significant reduction of vascularization compared with controls. Pellets containing bFGF and LM609 mAb induced significantly less neovascularization than pellets containing bFGF and control mAb.


CONCLUSIONS
Our results suggest that in the rat cornea, alpha(v)beta(3) ligation does inhibit bFGF-induced neovascularization. A chemical burn of the cornea induces angiogenisis which is not inhibited by blocking alpha(v)-integrins. This suggests an angiogenic pathway independent of alpha(v)-integrins.
Klotz
O
O
Franz Volhard Clinic at Max Delbrück Center for Molecular Medicine, Campus Buch, University Hospital Charité, Berlin, Germany.
Park
J K
JK
Pleyer
U
U
Hartmann
C
C
Baatz
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000187:drug effects*; D003315:Cornea / Q000187:drug effects; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000633:toxicity; D005455:Fluorescent Antibody Technique; D039564:Integrin alphaV; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000276:immunology; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D039564:Integrin alphaV; D016023:Integrins; D010456:Peptides, Cyclic; C092113:cyclo(arginyl-glycyl-aspartyl-phenylalanyl-valyl); D016222:Fibroblast Growth Factor 2