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G. M. Gordon, M. E. Fini; Roles for MMP-10 in Corneal Resurfacing. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6301.
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MMPs are known regulators and effectors of the corneal epithelial wound healing process. Recently, we have found that MMP-10 is strongly upregulated in the migrating corneal epithelium following wounding. We sought to determine the proliferative and migratory affects of MMP-10 in the corneal wound healing process by comparing these two parameters in MMP-10 knockout and wild type mice.
A 1mm trephine was used to demarcate the wound area in MMP-10 KO or c57 black wild type mice ages 6-8 weeks. An algerbrush II® was used to debride the corneal epithelium down to the basement membrane (without penetrating it) from the right eye of each mouse. To assess the role of MMP-10 on proliferation, eyes were enucleated at 18 and 24 hours post wounding, sectioned, and stained for ki67 or BrdU. To assess the role of MMP-10 on cell migration, wounds were visualized with a drop of fluorescine and imaged at the 0 and 18 hour time points. The rate of migration was determined by the % of the wound resurfaced after 18 hours as determined by image analysis software. Also, in order to get a more detailed picture of MMP-10 expression at 18 and 24 hours post-wounding, mRNA was harvested from migrating epithelial cells and quantitative real time PCR was performed.
MMP-10 showed an average fold increase of 26.3 and 9.6 at the 18 and 24 hour time points respectively, though the standard were as much or more than the average values indicating the varying nature of MMP expression by individual. . There was no significant difference found in the resurfacing rates of MMP-10 KO or wt mice. The wt mice resurfaced approximately 63% of the wound at 18 hours and 89% by 24 hours. MMP-10 KO mice exhibited a similar, though slightly slower migration rate with only about 60% resurfaced at 18 hours and 74% resurfaced at 24 hours. Proliferation was assessed in the migrating epithelial flap, the periphery of the wound, and the limbal region. Consistent with other findings, we found no proliferating cells in the migrating flap. Similarly, no significant difference in nuclear ki67 or BrdU signal was observed in the peripheral or limbal corneal epithelial cells by loss of MMP-10.
While there was a large variation in MMP-10 expression between individuals, the pattern of up-regulation remained the same for all mice examined. However, while MMP-10 was significantly up-regulated in corneal epithelial cells at both 18(resurfacing) and 24 hours (resurfaced) post wounding, we could find no significant effects on cell proliferation or migration rates. We did see a slight reduction in migration rates at both time points, but it was not significant and may be due to partial compensation by other MMPs. Also, MMP-10 may play a role in cell survival though this possibility remains to be studied.
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