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KMID : 0377519950200030237
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Chung-Ang Journal of Medicine
1995 Volume.20 No. 3 p.237 ~ p.252
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The Effect of Synthetic Inhibitor of Metalloproteinase on Corneal Alkali Burn in Rabbit
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Byon Do-Seok
Kim Jae-Chan
Shyn Kyung-Hwan
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Abstract
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Purpose of this study was to elucidate the effect of synthetic inhibitor of metalloproteinase(SIMP, HS-CH_2-R-CH(CH_2-CH(CH_3)_2-CO-Phe-Ala-NH_2; Peptides International, CO., USA), which is known to inhibit binding of Zn to zinc-dependent active site of metalloproteinases, on alkali burn in rabbit cornea. Thirty-six rabbits were included in this experiment, eighteen which received a 1 mM SIMP eyedrop every 2 hours(from 9:00 and 7:00 pm), and eighteen which received one drop of 10 mM phosphate buffered saline after 1 N NaOH application on central corneas for 60 seconds. The epithelial wound status was photographed twice a week, and metalloproteinases(72 and 92kDa gelatinase) were confirmed by SAD-PAGE and zymography, and their activities were measured by fluorometer once a week. At the same time, histopathologic examinations was performed on exciesed corneal specimens. The results were as follow : 1. The epithelial wound sizes of the SIMP treated group were statistically smaller than that of the control group(p<0.01). Recurrent epithelial break-down occured on post-burn 17 days. 2. Relative activities of the metalloproteinases of the control group were higher than that SIMP treated group(p<0.01), highest on post-burn 2 weeks and gradully decreased to post-burn 6 weeks. 3. According to the findings of SDS-PAGE and zymography, SIMP appeared to degrade 92kDa gelatinase directly and to inhibit activation of latent 74kDa gelatinase. 4. Light microscopic examination showed a more marked decrease of polymorphoneutrophils infiltration into the corneal stroma in SIMP treated group than that of the control group(p<0.01). As a conclusion, SIMP suppressed metalloproteinases, which are the most important tissue destructors on corneal alkali burn. And it suggests that SIMP inhibits PMN in filtration by reducing degraded products from collagen and suppresses PMN-induced MMP(72 & 92 gelatinase) activities.
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KEYWORD
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inhilitor of Metalloproteinase, corneal alkali burn, rabbit
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