The molecules in the corneal basement membrane zone affected by mustard exposure suggest potential therapies

Ann N Y Acad Sci. 2016 Aug;1378(1):158-165. doi: 10.1111/nyas.13226.


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.

Keywords: basement membrane zone; collagen XVII; cornea; mustard injury; mustard therapies; α6β4 integrin.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • ADAM17 Protein / antagonists & inhibitors
  • ADAM17 Protein / metabolism
  • Administration, Cutaneous
  • Animals
  • Basement Membrane / drug effects*
  • Basement Membrane / metabolism
  • Basement Membrane / pathology*
  • Chemical Warfare / trends
  • Cornea / drug effects*
  • Cornea / metabolism
  • Cornea / pathology*
  • Humans
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors / pharmacology*
  • Matrix Metalloproteinase Inhibitors / therapeutic use
  • Organ Culture Techniques


  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinase 9
  • ADAM17 Protein
  • ADAM17 protein, human