# Research Project II - Vesicant-Induced Corneal Injury

> **NIH NIH U54** · RBHS-SCHOOL OF PUBLIC HEALTH · 2020 · $388,378

## Abstract

Research Project 2. Vesicant-Induced Corneal Injury
Key Personnel:
Marion Gordon, Ph.D., Associate Professor, Rutgers University School of Pharmacy
Project Summary/Abstract
Sulfur mustard (SM) and nitrogen mustard (NM) cause microblistering injury to the cornea at the epithelial-
stromal border. When extensive, the epithelial layer sloughs off leading to long term consequences such as
recurrent corneal erosions and limbal stem cell deficiency. Our laboratories have been using a rabbit cornea
organ culture to analyze mechanisms underlying vesicant-induced injury to the cornea. We have discovered
that corneal injury after mustard exposure is due to activation of matrix metalloproteinases (MMPs), which
degrade the extracellular matrix of the basement membrane zone leading to separation of the epithelial layer
from the stroma; this is associated with delayed and defective wound healing. A major inducer of MMP
production is EMMPRIN (CD147), which we found is upregulated in the cornea following vesicant exposure.
EMMPRIN is known to be a receptor for cyclophillin A, an intracellular protein with proinflammatory activity,
released from cells following injury. We hypothesize that injury following mustard exposure is due to
cyclophillin A-induced inflammation and MMP activation by EMMPRIN. Furthermore, slower wound healing of
mustard-exposed corneas is due to delayed removal of provisional matrix, as well as delayed deposition of
fibronectin. To test these hypotheses, we will analyze the role of EMMPRIN and cyclophillin in MMP activation
in wound healing following mustard exposure. The effects of inhibiting the action of EMMPRIN using a
blocking antibody, and cyclophillin A using cyclosporine A (CsA) will be assessed. Improved healing will be
determined by a decrease in epithelial-stromal separation, decreased MMP9 activation and decreased IL-1
expression. We will also determine if prolonged corneal wound healing after mustard exposure is due to
delayed deposition of fibronectin (FN) which is required to support the cells' migration to close the injury. The
ability of a FN peptide known to promote corneal epithelial wound healing by facilitating migration will be
analyzed. Results of these studies will provide important mechanistic information on vesicant induced corneal
injury and may lead to the development of new therapies for treating mustard injury.

## Key facts

- **NIH application ID:** 9982791
- **Project number:** 5U54AR055073-15
- **Recipient organization:** RBHS-SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** MARION K GORDON
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $388,378
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982791

## Citation

> US National Institutes of Health, RePORTER application 9982791, Research Project II - Vesicant-Induced Corneal Injury (5U54AR055073-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9982791. Licensed CC0.

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