April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Corneal Vesciant Injury Is Ameliorated by Matrix Metalloproteinase Inhibitors
Author Affiliations & Notes
  • A. S. DeSantis
    Rutgers University, Piscataway, New Jersey
  • R. A. Hahn
    Pharmacology and Toxicology,
    Rutgers University, Piscataway, New Jersey
  • J. Beloni
    Pharmacology and Toxicology,
    Rutgers University, Piscataway, New Jersey
  • D. R. Gerecke
    Pharmacology and Toxicology,
    Rutgers University, Piscataway, New Jersey
  • K. K. H. Svoboda
    Biomedical Sciences, Baylor College of Dentistry, Dallas, Texas
  • M. K. Gordon
    Pharmacology and Toxicology,
    Rutgers University, Piscataway, New Jersey
  • G. Schultz
    Obstetrics and Gynecology, University of Florida, Gainesville, Florida
  • Footnotes
    Commercial Relationships  A.S. DeSantis, None; R.A. Hahn, None; J. Beloni, None; D.R. Gerecke, None; K.K.H. Svoboda, None; M.K. Gordon, None; G. Schultz, quickMed Technologies and Excaliard Pharmaceuticals, C.
  • Footnotes
    Support  NIH grant EY009056 and CounterACT Program NIAMS award U54 AR055073
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 3064. doi:
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      A. S. DeSantis, R. A. Hahn, J. Beloni, D. R. Gerecke, K. K. H. Svoboda, M. K. Gordon, G. Schultz; Corneal Vesciant Injury Is Ameliorated by Matrix Metalloproteinase Inhibitors. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3064.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Vesicants inflict injury to the corneal epithelial-stromal junction. Activation of matrix metalloproteinases (MMPs) may delay healing of vesicant wounds. Our goal was to characterize mild and moderate mustard injury in a rabbit corneal organ culture model system to determine whether the application of MMP inhibitors for 22 hr after injury would improve healing.

Methods: : Corneas were dissected from rabbit eyes (PelFreez) and placed in air lifted organ culture. Medium was added up to the corneal-scleral junction. Injuries were induced by applying 20 µl of 10 mM half mustard (CEES), or 10 µl of 10 mM nitrogen mustard to the central cornea. After 2 hours, medium was removed and replaced with either fresh medium or medium plus a counteragent, applying it dropwise to the central cornea. Such media were reapplied 3 times over the couse of the following 22 hours. Corneas were then analyzed by light or electron microscopy (EM).

Results: : 24 hr after exposures, suprabasal epithelial cell nuclei stained well with a modified H&E stain, but basal cells and their nuclei were paler than non-exposed controls. By EM, hemidesmosomes, the basement membrane and the anterior stromal ECM showed distinct signs of degradation. With the matrix metalloproteinase inhibitor Ilomastat, corneas showed improved basal cell-stromal adhesion after vesicant exposure, but adverse effects were not totally ameliorated. Treatment with the tetracycline derivatives sancycline and t-butyl sancycline improved histology on the mild mustard injury incurred by CEES exposure, but did not have a great effect on the moderate or severe nitrogen mustard injuries. Dedimethylamino tetracycline appeared to aggravate vesicant injury.

Conclusions: : Even mild mustard injury causes some degree of damage to the basal epithelial cells, the basement membrane and the stromal ECM. Sancycline, t-butyl sancycline and Ilomastat treatment improved histology of corneas after 24 hr compared to vesicant-exposed corneas that received no therapeutic agent.

Keywords: cornea: basic science • wound healing • ocular irritancy/toxicity testing 

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