Role of matrix metalloproteinases in failure to re-epithelialize after corneal injury

M. Elizabeth Fini, William C. Parks, William B. Rinehart, Marie T. Girard, Masao Matsubara, Jeffery R. Cook, Judith A. West-Mays, Peter M. Sadow, Robert E. Burgeson, John J. Jeffrey, Michael B. Raizman, Ronald R. Krueger, James D. Zieske

Research output: Contribution to journalArticle

169 Scopus citations

Abstract

Delayed re-epithelialization of the cornea after injury usually precedes stromal ulceration. Previous findings using a rat thermal injury model suggested that re-epithelialization is impeded by products of resident corneal cells, which destroy adhesive structures at the basement membrane zone. In this study, we provide additional evidence for this concept. Failure to re-epithelialize was found to correlate with an increase in the amounts of gelatinolytic matrix metalloproteinases present in the rat cornea. One of these gelatinases, gelatinase B, is synthesized by the resident corneal cells, and inhibition of its synthesis correlated with inhibition of basement membrane dissolution. The matrix metalloproteinases collagenase and stromelysin are also synthesized by resident corneal cells in thermally injured corneas of rabbits, but the timing of bulk enzyme synthesis correlated more closely with deposition of repair tissue in the stroma than with failure to re-epithelialize. Nevertheless, in human corneas with repair defects, gelatinase B and collagenase are synthesized by cells in the basal layer of the epithelium directly adjacent to the basement membrane, suggesting that both could participate in dissolution of this structure. Importantly, treatment of thermally injured corneas with a synthetic inhibitor of matrix metalloproteinases significantly improved basement membrane integrity. These data support the concept that over-expression of matrix metalloproteinases by resident corneal cells impedes re- epithelialization after some types of corneal injury.

Original languageEnglish (US)
Pages (from-to)1287-1302
Number of pages16
JournalAmerican Journal of Pathology
Volume149
Issue number4
StatePublished - Oct 1996

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Role of matrix metalloproteinases in failure to re-epithelialize after corneal injury'. Together they form a unique fingerprint.

  • Cite this

    Fini, M. E., Parks, W. C., Rinehart, W. B., Girard, M. T., Matsubara, M., Cook, J. R., West-Mays, J. A., Sadow, P. M., Burgeson, R. E., Jeffrey, J. J., Raizman, M. B., Krueger, R. R., & Zieske, J. D. (1996). Role of matrix metalloproteinases in failure to re-epithelialize after corneal injury. American Journal of Pathology, 149(4), 1287-1302.