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Gabriel Sosne, Patricia L. Christopherson, Ronald P. Barrett, Rafael Fridman; Thymosin-β4 Modulates Corneal Matrix Metalloproteinase Levels and Polymorphonuclear Cell Infiltration after Alkali Injury. Invest. Ophthalmol. Vis. Sci. 2005;46(7):2388-2395. doi: 10.1167/iovs.04-1368.
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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.
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