Wednesday, December 24, 2025 12/24/2025

Identification of a new role of membrane‐type 1 matrix metalloproteinases in corneal neovascularization

Award Number: R01EY033758
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2027

Group Awards By:

View Award Description

Identification of a new role of membrane‐type 1 matrix metalloproteinases in corneal neovascularization - Project Summary/Abstract Corneal neovascularization (NV) can be caused by severe corneal injury or infection and is a leading cause of blindness. Balance of pro-angiogenic factors and anti-angiogenic factors are important to maintain avascular corneal tissue. Pro-angiogenic factors such as VEGFA and FGF2 are highly induced in inflamed corneas and lead to activation of its receptor proteins such as VEGFR2 and FGFR2. Membrane-type 1 matrix metalloproteinase (MMP-14) is involved in remodeling of extracellular matrix (ECM) through its proteolytic activity. Recent studies have revealed that MMP-14 is a regulator of VEGFA/VEGFR2-mediated corneal NV via unique and selective cleavage of VEGFR1 which is a decoy receptor for VEGFR2. FGF2-induced corneal NV is delayed in MMP-14 knockout (KO) mice, indicating there is some correlation between FGF2 and MMP-14. However, how MMP-14 interacts with FGF2 is still largely unknown. The goal of this application is to characterize mechanism of MMP-14 on regulation of FGFR2 levels via ADAM-9 enzyme. We demonstrated that FGFR2 level was low in MMP-14 KO corneal fibroblast cells. On the other hand, ADAM-9, which is substrate of MMP-14, was higher in MMP-14 KO fibroblast than WT cells. We have also discovered that expression of MMP-8, MMP-9, and ADAM-17, all of which are underlying FGF2/FGFR2-system, were highly induced in WT than MMP-14 KO cells upon stimulation of FGF2. Thus, inhibition of MMP-14 can reduce FGF2/FGFR2-mediated corneal NV and inflammation. Furthermore, our results show that FDA-approved small molecule drugs, clioquinol, chloroxine, and folic acid, all of which contain a quinoline scaffold, inhibit MMP-14 enzyme activity. We propose three specific aims: (1) Mechanism of two enzyme cascades, MMP-14 and ADAM-9, to regulate FGFR2 level and expression of FGF2/FGFR2-mediated MMPs; (2) investigate the effect of MMP-14 in FGF2/FGFR2-mediated corneal inflammation; (3) Characterize quinoline analogs as selective MMP-14 inhibitors. We will complete these aims using innovative techniques from molecular biology and biophysics in vitro and in vivo.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $399,750 )
2026	2026	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Vision Research	000	4	12/8/2025	NON-COMPETING CONTINUATION	$399,750
														Subtotal = $399,750

Issue Date FY: 2025 ( Subtotal = $399,750 )
2025	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Vision Research	000	3	11/27/2024	NON-COMPETING CONTINUATION	$399,750
														Subtotal = $399,750

Issue Date FY: 2024 ( Subtotal = $399,750 )
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Vision Research	000	2	11/30/2023	NON-COMPETING CONTINUATION	$399,750
														Subtotal = $399,750

Issue Date FY: 2023 ( Subtotal = $399,750 )
2023	2023	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Vision Research	000	1	12/21/2022	NEW	$399,750
														Subtotal = $399,750

Grand Total All Awards = $1,599,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Identification of a new role of membrane‐type 1 matrix metalloproteinases in corneal neovascularization

Award Number: R01EY033758

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/01/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer