title: The molecules in the corneal basement membrane zone affected by mustard exposure suggest potential therapies.
abstract: Mustard exposures result in epithelial-stromal separations in the cornea and epidermal-dermal separations in the skin. Large blisters often manifest in skin, while the cornea develops microblisters, and, when enough form, the epithelium sloughs. If the exposure is severe, healing can be imperfect and can result in long-term adverse consequences. For the cornea, this could manifest as recurrent corneal erosions. Since the corneal epithelial-stromal separations are in the region identified by electron microscopy as the lamina lucida, the same region affected by the blistering disease junctional epidermolysis bullosa (JEB), we postulated that the molecules that are defective in JEB would be the same ones cleaved by mustard compounds. These molecules are α6β4 integrin and collagen XVII, which can be cleaved by matrix metalloproteinase-9 (MMP-9) and ADAM17, respectively. Therefore, our laboratory has tested MMP-9 and ADAM17 inhibitors as potential therapies to attenuate corneal mustard injury. Our results demonstrated that inhibiting MMP-9 and ADAM17 resulted in less epithelial-stromal separation in the corneas at 24 h postexposure, as compared with using only medium as a therapy.
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey. magordon@eohsi.rutgers.edu.
authors.forename: Marion K
authors.initials: MK
authors.lastname: Gordon
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey.
authors.forename: Andrea
authors.initials: A
authors.lastname: DeSantis-Rodrigues
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey.
authors.forename: Rita
authors.initials: R
authors.lastname: Hahn
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey.
authors.forename: Peihong
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey.
authors.forename: Yokechen
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Biomedical Sciences, Baylor College of Dentistry, Texas A&M Health Science Center, Dallas, Texas.
authors.forename: Kathy K H
authors.initials: KK
authors.lastname: Svoboda
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Gerecke
mesh_terms: D000072198:ADAM17 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D000279:Administration, Cutaneous; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D002618:Chemical Warfare / Q000639:trends; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D009924:Organ Culture Techniques
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D020780:Matrix Metalloproteinase 9; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
keywords: basement membrane zone; collagen XVII; cornea; mustard injury; mustard therapies; α6β4 integrin