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The corneal epithelium in sulfur mustard ocular injury-In vitro and ex vivo studies

TitleThe corneal epithelium in sulfur mustard ocular injury-In vitro and ex vivo studies
Publication TypeConference Proceedings
Year of Conference2004
AuthorsAmir A., Dachir S., Cohen L., Cohen M., Gutman H., Shalem Y., Kadar T.
Conference NameProceedings of the U.S. Army Medical Defense Bioscience Review
Volume198
Pagination1-10
Conference LocationAberdeen Proving Ground, MD
Abstract

Sulfur Mustard (HD) induced acute ocular lesions are characterized by corneal epithelial erosions, anterior segment inflammation, deterioration of corneal nerves, and keratocyte apoptosis (all shown in our rabbit animal model). Corneal epithelial erosions develop over the first days, peak at about 48 hrs, and are apparently healed at 1 week. This is in contrast with other chemical exposures (alkali, heptanol) where erosions are evident immediately upon exposure. At the peak of corneal erosions only about 10-20% of the cornea shows fluorescein-stained areas covering mainly the central part of the cornea even though the whole cornea was exposed to the vapor. The present work aimed to study the initial reaction of corneal epithelial cells to HD exposure in the SIRC cell line and in primary cultures obtained from corneal explants (PRCEC), and the proliferation of epithelial cells at various times after in vivo HD exposure (ex- vivo cultures). Cells were exposed in vitro to HD (10-600μM), cell proliferation was followed for severaldays and inflammatory mediator release was measured. Ex- vivo cultures were observed forrate of cell outgrowth from the explant, for cell yield and for growth of 1st passage cultures.HD exposure caused a dose dependent inhibition of proliferation with 50% inhibition at~150uM and 10uM at 2-6hrs and at 24 hrs respectively, and cell death at higher doses.However, even at HD concentrations that did not cause a decrease in cell number, distinctmorphological changes were noticed. MTT growth curves showed that SIRC cells were lesssensitive to HD than PRCEC cells. Cells reacted to HD exposure by releasing PGE in a dosedependent manner.Ex- vivo explants obtained from the center of severely damaged corneas at the acute stageof the lesion practically did not grow to form monolayers. There was some sporadicabnormal cell growth. Explants obtained from corneas when corneal erosions were healed,had a decreased rate of cell outgrowth and lower yields of cells were obtained. The 1stpassage cultures showed attenuation of growth.It is concluded that an acute reaction to HD exposure was a dose-dependent cell growtharrest, which could explain the postponed appearance of corneal erosions, and that epithelialcells contributed to the anterior segment inflammation by releasing PGE. The regeneratedepithelium was damaged and had lower proliferation potential than epithelial cells fromnaïve corneas. It is hypothesized that long term effects derived in part from improper regeneration of corneal epithelium.

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