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(Investigative Ophthalmology and Visual Science. 2005;46:2388-2395.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.04-1368
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Thymosin-ß4 Modulates Corneal Matrix Metalloproteinase Levels and Polymorphonuclear Cell Infiltration after Alkali Injury

Gabriel Sosne,1,2 Patricia L. Christopherson,1 Ronald P. Barrett,2 and Rafael Fridman3

1From the Department of Ophthalmology, Kresge Eye Institute, Detroit, Michigan; and the 2Departments of Anatomy and Cell Biology and 3Pathology, Wayne State University, Detroit, Michigan.

PURPOSE. Corneal alkali injury is highly caustic, and present clinical therapies are limited. The purpose of this study was to investigate the ability of thymosin-ß4 (Tß4) to promote healing in an alkali injury model and the mechanisms involved in that process.

METHODS. Corneas of BALB/c mice were injured with NaOH, irrigated copiously with PBS, and treated topically with either Tß4 or PBS twice daily. At various time points after injury (PI), corneas from the Tß4- versus the PBS-treated group were examined for polymorphonuclear leukocyte (PMN) infiltration, chemokine, and matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) expression.

RESULTS. Tß4-treated corneas demonstrated improved corneal clarity at day 7 PI. Whereas Tß4 decreased corneal MMP-2 and -9 and MT6-MMP levels after alkali injury, no change in TIMP-1 and -2 expression was detected. Tß4 treatment also decreased corneal KC (CXCL1) and macrophage inflammatory protein (MIP)-2 chemokine expression and PMN infiltration. Immunohistochemistry studies demonstrated MMP-9 expression at the leading edge of the epithelial wound, in the the limbus (containing stem cells), and in stromal PMNs.

CONCLUSIONS. Tß4 treatment decreases corneal inflammation and modulates the MMP/TIMP balance and thereby promotes corneal wound repair and clarity after alkali injury. These results suggest that Tß4 may be useful clinically to treat severe inflammation-mediated corneal injuries.




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