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A. Petznick, M. D. M. Evans, M. C. Madigan, Q. Garrett, D. F. Sweeney; Production of Mmp-1, -9 and Timp-1 by Corneal and Conjunctival Epithelium in a Cat Model of Corneal Wound Healing. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6309.
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To determine whether the corneal and conjunctival epithelium produce matrix-metalloproteinase-1 and -9 (MMP-1 and -9) and an inhibitor (tissue inhibitor metalloproteinase -1 (TIMP-1)) following corneal epithelial debridement in a cat model.
A 9-mm diameter central corneal wound was created on one eye of 8 cats by epithelial debridement. Unwounded eyes of 2 other cats served as controls. Eyes were removed at the each time point (0, 24 and 48 hours, and 2 weeks post-wounding), fixed in formalin and paraffin-embedded for immunohistochemical detection of MMP-1, -9 and TIMP-1 using peroxidase. Immunoreactivity was graded. PAS staining for mucin-containing goblet cells was performed.
MMP-1 and -9 immunoreactivity increased in the cornea in response to wounding, as seen previously in debridement models, however production of MMP-1 in the stroma was not seen in our feline model. MMP-1, -9 and TIMP-1 were upregulated in the corneal epithelium in a time-dependent manner, with a peak at 24 hours after debridement. During epithelial migration and following establishment of an intact epithelial monolayer (24 to 48 hours post-wounding), we also found MMP-1 and -9 upregulation in the conjunctival epithelium. Goblet cells expressed MMP-1 and -9 immunoreactivity at all time-points except at 48 hours post-wounding. Specificity of MMP-1 and -9 immunoreactivity in these cells was confirmed with appropriate controls. An absence of conjunctival PAS-staining at 48 hours post-wounding (when MMP immunoreactivity was absent) suggested the disappearance of goblet cells or at least, loss of mucin and MMP producing potential.
These studies confirm the involvement of MMP-1, -9 and TIMP-1 in epithelial wound closure following debridement, related to epithelial migration and subsequent restratification of cells. Interestingly, we note for the first time the presence of MMP-1 and -9 in goblet cells in normal tissue.
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