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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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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.
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).
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.
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.
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