Inhibition of Basic Fibroblast Growth Factor Induced Corneal Angiogenesis by a Urokinase Plasminogen Activator Receptor Antagonist.
- Author:
Sung Kun CHUNG
1
;
Ja Young LEE
;
David G HWANG
Author Information
1. Department of Ophthalmology, Catholic University, Medical College, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Angiogenesis;
Corneal pocket assay;
Urokinase plasminogen activator receptor antagonist
- MeSH:
Cornea;
Corneal Neovascularization*;
Endothelial Cells;
Endothelial Growth Factors;
Fibroblast Growth Factor 2*;
Fibroblasts;
Hydrogel;
Immunoglobulin G;
New Zealand;
Plasminogen Activators*;
Plasminogen*;
Urokinase-Type Plasminogen Activator*
- From:Journal of the Korean Ophthalmological Society
1996;37(10):1595-1600
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
During angiogenesis, expression of urokinase plasminogen activator(uPA) and its receptor(uPAR) is upregulated in vascular endothelial cells. Binding of uPA to uPAR has been implicated as an important component of the angiogenesis pathway and represents a potential target for the design of anti-angiogenic compounds. We have produced a high-affinity competitive antagonist for the uPA receptor consisting of a fusion protein linking the endothelial growth factor (EGF)-like domain of uPA (residues 1-48) to the Fc domain of IgG. To determine whether this recombinant murine uPA(1-48)-IgG fusion protein could interfere with angiogenesis we studied the effect of this compound on rabbit corneal angiogenesis induced by basic fibroblast growth factor(bFGF). A hydrogel disk containing 1000ng of bFGF was implanted intrastromally into the superior cornea of each of sixteen New Zealand white rabbit eyes. All eyes received a second intrastromal disk, randomized to contain either 35 microgram of uPA(1-48)-IgG fusion protein(n=8) or phosphate-buffered saline(PBS)(n=8). Both disks were positioned side-by-side, 1.2 mm from the superior limbus. At three days post-implantation of bFGF disks, eyes treated with uPA(1-48)-IgG fusion protein had reduced angiogenesis(mean score=2.2) compared to PBS-treated controls (mean score=5.1)(p<0.05, Wilcoxon rank sum test). In a rabbit corneal pocket assay, murine uPA(1-48)-IgG fusion protein appears to inhibit bFGF-induced angiogenesis. Compounds that block uPAR binding of uPA may have therapeutic potential as anti-angiogenic agents.
