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T Kato, S Saika, Y Ohnishi; Effect of a Metalloproteinase Inhibitor on Composition of Type IV Collagen Alpha Chain in Epithelial Basement Membrane of Alkali-burned Rabbit Cornea . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4208.
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Purpose:To examine the effect of of a metalloproteinase inhibitor (MMPI) on composition of type IV collagen alpha(α) chain in epithelial basement membrane (BM) of alkali-burned rabbit cornea. Methods:(1) A central cornea (6 mm in diameter) of albino rabbits was exposed to a 1N NaOH for 3 min. The MMPI (GM6001, 0.5 mg/0.5 ml) was subconjunctivally injected and allowed to heal for 3 (n=3) or 7 (n=3) days. Vehicle was administered in control animals. Cryosections of affected corneas were immunostained for α1-α2 of collagen IV or α5 chain. (2) Alkali-burned cornea was organ-cultured in the presence or absence of MMPI for 3 or 7 days and then similarly immunostained. (3) Effect of MMPI on migration of corneal epithelium was finally assayed in organ-culture. Results:(1) Uninjured corneal epithelial BM exhibited α5-immunoreactivity, but lacked α1 and α2 of collagen IV. Both MMPI- and vehicle-treated corneas were re-epithelialized at Day 3. α5-positive BM disappeared and α1- and α2-immunoreactivities were detected in control corneas at Days 3 and 7, whereas α5-positive and α1, α2-negative BM was observed at Days 3 and 5 in MMPI-treated corneas. (2) Results from organ-culture experiments were similar to those from in vivo study at the concentration of 5 µg/ml. (3) Excessive MMPI (5 µg/ml) decreased migration of epithelium of organ-cultured corneas. Conclusion:MMPI suppresses degradation corneal epithelial BM during healing following an alkali burn, resulting in the maintenance of α chain composition. Excessive MMPI, however, may decrease reepithelialization.
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