# Metalloproteinase Expression in Corneal Wounds

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $399,750

## Abstract

Corneal neovascularization (NV) is a major cause of blindness worldwide. Toward the overall
goal of identifying a molecular target for blocking corneal NV, the objective of the proposed
research is to determine the role of membrane type 1 matrix metalloproteinase (MT1-MMP)
activity, and specifically its proteolytic functions, in corneal NV. Our laboratory has found that
MT1-MMP increases vascular endothelial growth factor (VEGF)-A–induced ERK
phosphorylation in a time- and concentration-dependent manner in vascular endothelial cells.
Aortic ring assays showed diminished vessel sprouting in vitro in response to VEGF-A
stimulation, but not to basic fibroblast growth factor (bFGF) stimulation, in mice with conditional
deletion of vascular MT1-MMP as compared to that in control mice. In addition, diminished
VEGF-A–induced corneal angiogenesis was seen in vivo in mice with conditional deletion of
vascular MT1-MMP compared with that in control mice. We hypothesize that limbal
microvascular endothelial cell-associated MT1-MMP is required for VEGF-A–mediated corneal
NV and that MT1-MMP promotes corneal NV by three novel mechanisms: (i) MT1-MMP binds to,
and degrades, VEGF receptor 1 (VEGFR1) on limbal microvascular endothelial cells (Aim A); (ii)
MT1-MMP degradation of VEGFR1 on invading limbal microvascular endothelial
cells potentiates pro-MMP2 activation and thereby increases its collagenolytic activity (Aim B);
and (iii) enzymatically-active MT1-MMP tethered to stromal fibroblast-derived exosomes
promotes VEGFR1 degradation on limbal vascular endothelial cells (Aim C). Spatial and
temporal characterization of MT1-MMP activity in corneal angiogenesis and evaluation of the
proposed mechanisms of corneal NV will be valuable for the treatment of corneal NV and for
identifying potential targets for therapeutic intervention in ocular and systemic conditions
involving angiogenesis.

## Key facts

- **NIH application ID:** 9910393
- **Project number:** 5R01EY010101-24
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Dimitri T Azar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,750
- **Award type:** 5
- **Project period:** 1993-12-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9910393

## Citation

> US National Institutes of Health, RePORTER application 9910393, Metalloproteinase Expression in Corneal Wounds (5R01EY010101-24). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9910393. Licensed CC0.

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