Abstract

Background: Corneal neovascularization is a major cause of blindness worldwide. The objective of our research is to identify the role of collagen XVIII and its proteolytic fragments in corneal neovascularization. Our laboratory has found that MMP-7 cleaves corneal and recombinant collagen XVIII to generate a 28 kDa fragment which may regulate corneal neovascularization during corneal wound healing. Hypothesis: Activated MMP-7 in cornea may contribute to the production of endostatin and endostatin-spanning fragments, which inhibit corneal neovascularization.
Specific Aims : A. To determine the distribution of endostatin and MMP-7-derived proteolytic fragment of collagen XVIII in the cornea in vivo and in vitro. B. To characterize the function of endostatin and MMP-7-derived proteolytic fragment of collagen XVIII in vascular endothelial cell proliferation, migration, and tube formation in vitro. C. To characterize the role of endostatin and MMP-7-derived proteolytic fragment of collagen XVIII in corneal neovascularization in vivo. Significance: Understanding the mechanisms that maintain corneal avascularity may allow us to prevent blindness caused by corneal neovascularization. The study of endostatin and MMP-7 in the cornea may provide valuable information about their possible clinical significance in corneal neovascularization and wound healing.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
7R01EY014048-04
Application #
7239024
Study Section
Special Emphasis Panel (ZRG1-VISA (01))
Program Officer
Fisher, Richard S
Project Start
2003-08-01
Project End
2007-07-31
Budget Start
2006-06-01
Budget End
2006-07-31
Support Year
4
Fiscal Year
2005
Total Cost
$148,610
Indirect Cost

  Institution

Name
University of Illinois at Chicago
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612

  Publications

(2012) Retraction. MT1-MMP cleavage of the antiangiogenic proteoglycan decorin: role in corneal angiogenesis: retraction. Cornea 31:467
Mimura, Tatsuya; Chang, Jin-Hong; Kim, Tae-Im et al. (2011) MT1-MMP cleavage of the antiangiogenic proteoglycan decorin: role in corneal angiogenesis. Cornea 30 Suppl 1:S45-9
Yeh, Shu-I; Han, Kyu-Yeon; Sabri, Abdellah et al. (2010) MMP-7 knock-in corneal fibroblast cell lines secrete MMP-7 with proteolytic activity towards collagen XVIII. Curr Eye Res 35:799-805
Azar, Dimitri T; Casanova, Fabio H; Mimura, Tatsuya et al. (2010) Corneal epithelial MT1-MMP inhibits vascular endothelial cell proliferation and migration. Cornea 29:321-30
Oliveira, Hailton B; Sakimoto, Tohru; Javier, Joel A D et al. (2010) VEGF Trap(R1R2) suppresses experimental corneal angiogenesis. Eur J Ophthalmol 20:48-54
Ellenberg, David; Azar, Dimitri T; Hallak, Joelle A et al. (2010) Novel aspects of corneal angiogenic and lymphangiogenic privilege. Prog Retin Eye Res 29:208-48
Mimura, Tatsuya; Han, Kyu Yeon; Onguchi, Tatsuya et al. (2009) MT1-MMP-mediated cleavage of decorin in corneal angiogenesis. J Vasc Res 46:541-50
Onguchi, Tatsuya; Han, Kyu Yeon; Chang, Jin-Hong et al. (2009) Membrane type-1 matrix metalloproteinase potentiates basic fibroblast growth factor-induced corneal neovascularization. Am J Pathol 174:1564-71
Azar, Dimitri T; Casanova, Fabio H; Mimura, Tatsuya et al. (2008) Effect of MT1-MMP deficiency and overexpression in corneal keratocytes on vascular endothelial cell migration and proliferation. Curr Eye Res 33:954-62
Sakimoto, Tohru; Kim, Tae-Im; Ellenberg, David et al. (2008) Collagen XVIII and corneal reinnervation following keratectomy. FEBS Lett 582:3674-80

Showing the most recent 10 out of 16 publications