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

Marion K. Gordon, Andrea DeSantis-Rodrigues, Rita Hahn, Peihong Zhou, Yokechen Chang, Kathy K.H. Svoboda, Donald R. Gerecke

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)158-165
Number of pages8
JournalAnnals of the New York Academy of Sciences
Volume1378
Issue number1
DOIs
StatePublished - Aug 1 2016

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Keywords

  • basement membrane zone
  • collagen XVII
  • cornea
  • mustard injury
  • mustard therapies
  • α6β4 integrin

Fingerprint

Dive into the research topics of 'The molecules in the corneal basement membrane zone affected by mustard exposure suggest potential therapies'. Together they form a unique fingerprint.

Cite this