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A. Amir, S. Dachir, L. Cohen, M. Cohen, H. Gutman, Y. Shalem, T. Kadar; Corneal Epithelial Cell Reaction to Sulfur Mustard Exposure Contributes to the Acute Anterior Segment Inflammation and to the Development of Epithelial Lesions . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2151.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Sulfur Mustard (SM) induced ocular lesions are clinically characterized, by acute and late corneal epithelial defects, anterior segment inflammation and deterioration of corneal nerves. This work aimed to study the reaction of corneal epithelial cells to SM exposure using three in vitro models: 1.SIRC corneal cell line. 2. Primary corneal epithelial cells grown from explant cultures of naïve rabbit corneas (PRCEC). 3. PRCEC taken from explants of in vivo exposed rabbit corneas– ex vivo. Methods: Animal Care and Use Committee (ACUC) approval at IIBR was obtained. SIRC cells were from ATCC. Rabbit eyes were exposed to SM vapor and a clinical follow up was carried out. At 24 hrs, 1,2 and 3 weeks following exposure, corneas (4–8/time point) were taken for culture. PRCEC were grown using adaptation of published methods. Cell proliferation following in vitro SM exposure was quantitated by 3H–thymidine incorporation and culture growth by MTT reaction. Secretion of PGE was measured by RIA. Proliferative capacity of ex–vivo explants was measured from explant outgrowth, and from growth of 1st passage cultures. Results: In vitro SM exposure caused a dose dependent inhibition of proliferation with 50% inhibition at ∼150uM and 10uM at 2–6hrs and at 24 hrs respectively for SIRC and PRCEC. MTT growth curves also showed that SIRC cells were less sensitive to SM than PRCEC cells. Both SIRC and PRCEC reacted to SM exposure by releasing PGE in a dose dependent manner. PGE release in PRCEC was enhanced by the neurogenic factor CGRP (5–10nM). Ex– vivo explants obtained from severely damaged corneas 24 hrs after exposure practically did not grow to form monolayers. Explants obtained from corneas 1–3 weeks after SM exposure, when corneal erosions seemed clinically healed, had a decreased rate of cell outgrowth. 1st passage ex vivo cultures also showed attenuation of growth. Conclusions: Cell growth arrest and cell death following SM exposure could explain the postponed appearance of corneal erosions observed clinically. Epithelial cells contribute to the anterior segment inflammation by releasing PGE upon SM exposure. This secretion can be augmented by nerve deterioration releasing neurogenic factors. The damage and lower proliferation potential of the regenerated epithelium suggests that long term effects following SM exposure derived in part from improper regeneration of corneal epithelium.
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