J Korean Ophthalmol Soc.  1996 Oct;37(10):1595-1600.

Inhibition of Basic Fibroblast Growth Factor Induced Corneal Angiogenesis by a Urokinase Plasminogen Activator Receptor Antagonist

• Chung SK
• Lee JY
• Hwang DG

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.

Keyword

Angiogenesis; Corneal pocket assay; Urokinase plasminogen activator receptor antagonist

MeSH Terms

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*
Endothelial Growth Factors
Fibroblast Growth Factor 2
Hydrogel
Immunoglobulin G
Plasminogen
Plasminogen Activators
Urokinase-Type Plasminogen Activator