Background: Corneal neovascularization is a major cause of blindness worldwide. The objective of our research is to identify the role of membrane type 1 matrix metalloproteinase (MT1-MMP) and its proteolytic functions in corneal neovascularization. Our laboratory has found that MT1-MMP is present in the cornea and cleaves anti-angiogenic fragments which may regulate corneal neovascularization during corneal wound healing. Hypothesis: During corneal wounding, stromal fibroblasts generate membrane-type matrix metalloproteinase (MT1-MMP), which mediates corneal neovascularization (NV) by three mechanisms: breakdown of the extracellular matrix (ECM), degradation of corneal anti-angiogenic factors, and transcriptional up-regulation of vascular endothelial growth factor (VEGF).
Specific aims : A. MT1-MMP Distribution and Enzymatic Activity in Corneal Neovascularization. B. Evaluation of 1st Pathway of Corneal Angiogenesis: ECM Breakdown by Keratotocyte Membrane-Associated MT1-MMP. C. Evaluation of the 2nd Pathway of Corneal Angiogenesis: Keratocyte-derived MT1-MMP Degradation of Corneal Anti-angiogenic Factors. D. Evaluation of the 3rd Pathway of Corneal Angiogenesis: MT1-MMP-Induced Transcriptional Upregulation of VEGF in Stromal Keratocytes. Significance: Understanding the mechanisms that maintain corneal avascularity may allow us to prevent blindness caused by corneal neovascularization. The study of MT1-MMP in the cornea may provide valuable information about their possible clinical significance in corneal neovascularization and wound healing.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY010101-11
Application #
6619208
Study Section
Special Emphasis Panel (ZRG1-VISA (01))
Program Officer
Fisher, Richard S
Project Start
1993-12-01
Project End
2008-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
11
Fiscal Year
2003
Total Cost
$418,500
Indirect Cost
Name
Schepens Eye Research Institute
Department
Type
DUNS #
073826000
City
Boston
State
MA
Country
United States
Zip Code
02114
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