Sulfur Mustard Corneal Injury Is Associated With Alterations in the Epithelial Basement Membrane and Stromal Extracellular Matrix

Authors

Laurie B. Joseph, Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, United States of America. Electronic address: lbjoseph@pharmacy.rutgers.edu.
Marion K. Gordon, Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, United States of America.
Peihong Zhou, Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, United States of America.
Rita A. Hahn, Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, United States of America.
Hamdi Lababidi, Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, United States of America.
Claire R. Croutch, MRIGlobal, Kansas City, MO 64110, United States of America.
Patrick J. Sinko, Department of Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, United States of America.
Diane E. Heck, Department of Public Health, New York Medical College, Valhalla, NY 10595, United States of America.
Debra L. Laskin, Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, United States of America.
Jeffrey D. Laskin, Department of Environmental and Occupational Health and Justice, Rutgers University School of Public Health, Piscataway, NJ 08854, United States of America.

Author Type(s)

Faculty

DOI

10.1016/j.yexmp.2022.104807

Journal Title

Experimental and Molecular Pathology

First Page

104807

Document Type

Article

Publication Date

10-1-2022

Department

Public Health

Abstract

Sulfur mustard (SM; bis(2-chloroethyl) sulfide) is a highly reactive bifunctional alkylating agent synthesized for chemical warfare. The eyes are particularly sensitive to SM where it causes irritation, pain, photophobia, and blepharitis, depending on the dose and duration of exposure. In these studies, we examined the effects of SM vapor on the corneas of New Zealand white male rabbits. Edema and hazing of the cornea, signs of acute injury, were observed within one day of exposure to SM, followed by neovascularization, a sign of chronic or late phase pathology, which persisted for at least 28 days. Significant epithelial-stromal separation ranging from ~8-17% of the epithelial surface was observed. In the stroma, there was a marked increase in CD45 leukocytes and a decrease of keratocytes, along with areas of disorganization of collagen fibers. SM also disrupted the corneal basement membrane and altered the expression of perlecan, a heparan sulfate proteoglycan, and cellular fibronectin, an extracellular matrix glycoprotein. This was associated with an increase in basement membrane matrix metalloproteinases including ADAM17, which is important in remodeling of the basement membrane during wound healing. Tenascin-C, an extracellular matrix glycoprotein, was also upregulated in the stroma 14-28 d post SM, a finding consistent with its role in organizing structural components of the stroma necessary for corneal transparency. These data demonstrate that SM vapor causes persistent alterations in structural components of the cornea. Further characterization of SM-induced injury in rabbit cornea will be useful for the identification of targets for the development of ocular countermeasures.

Recommended Citation

Joseph, L. B., Gordon, M. K., Zhou, P., Hahn, R. A., Lababidi, H., Croutch, C. R., Sinko, P. J., Heck, D. E., Laskin, D. L., & Laskin, J. D. (2022). Sulfur Mustard Corneal Injury Is Associated With Alterations in the Epithelial Basement Membrane and Stromal Extracellular Matrix. Experimental and Molecular Pathology, 128, 104807. https://doi.org/10.1016/j.yexmp.2022.104807