Thymosin- 4 Modulates Corneal Matrix Metalloproteinase Levels and Polymorphonuclear Cell Infiltration after Alkali Injury

Abstract

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-β4 (Τβ₄) 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 Tβ₄ or PBS twice daily. At various time points after injury (PI), corneas from the Tβ₄- versus the PBS-treated group were examined for polymorphonuclear leukocyte (PMN) infiltration, chemokine, and matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) expression. results. Tβ₄-treated corneas demonstrated improved corneal clarity at day 7 PI. Whereas Tβ₄ decreased corneal MMP-2 and -9 and MT6-MMP levels after alkali injury, no change in TIMP-1 and -2 expression was detected. Tβ₄ 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. Tβ₄ 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 Tβ₄ may be useful clinically to treat severe inflammation-mediated corneal injuries.