May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Thymosin ß4 Modulates Corneal Matrix Metalloproteinase Expression and Neutrophil Infiltration After Alkali Injury in the BALB/c Mouse
Author Affiliations & Notes
  • P.L. Christopherson
    Ophthalmology, Kresge Eye Institute, Detroit, MI
  • R. Fridman
    Pathology,
    Wayne State University, Detroit, MI
  • R.P. Barrett
    Anatomy/Cell Biology,
    Wayne State University, Detroit, MI
  • G. Sosne
    Ophthalmology and Anatomy/Cell Biology,
    Wayne State University, Detroit, MI
  • Footnotes
    Commercial Relationships  P.L. Christopherson, None; R. Fridman, None; R.P. Barrett, None; G. Sosne, None.
  • Footnotes
    Support  KO8 EY13412
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 1414. doi:
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      P.L. Christopherson, R. Fridman, R.P. Barrett, G. Sosne; Thymosin ß4 Modulates Corneal Matrix Metalloproteinase Expression and Neutrophil Infiltration After Alkali Injury in the BALB/c Mouse . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1414.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: The purpose of this study was to determine the effect of thymosin beta 4 (Tß4) on the expression of matrix metalloproteinases (MMP) and on polymorphonuclear cells (PMN) infiltration during corneal tissue remodeling after alkali burn in BALB/c mice. Methods: Corneas from BALB/c mice were burned with a 2 mm disc soaked in 1 N NaOH for 30 seconds. Eyes were irrigated copiously with PBS and treated topically with either Tß4 (5 µg/5 µl PBS) or 5 µl PBS twice daily. At 1, 3 and 7 days, mice were sacrificed, the eyes grossly examined and enucleated, and the corneas from the Tß4 vs PBS–treated groups (n=5/group/timepoint) were processed for mRNA, protein (ELISA), immunohistochemistry (IHC), myeloperoxidase (MPO) and zymogram analyses. Experiments were repeated in triplicate. Results:4–treated corneas demonstrated decreased inflammation and hyphema at 7 days after injury when compared to PBS–treated controls. MPO values, correlating with the number of PMNs present in the corneas, were markedly decreased in the Tß4–treated corneas at 3 and 7 days after injury compared to PBS–treated corneas. Following analysis of RT–PCR results, Tß4–treated corneas exhibited decreased gene transcript levels for chemokines: macrophage inflammatory protein (MIP)–2 at 1 day and chemokine ligand 1 (Cxcl1, KC) at 3 and 7 days after injury. The Tß4–treated corneas demonstrated a marked decrease in MMP–9 gene transcript and protein levels at 3 and 7 days after injury. In addition, MMP–9 protein expression was localized by IHC and was found mostly in the corneal epithelium in both groups although the Tß4–treated corneas showed a stronger staining in the limbus compared to the PBS–treated eyes at day 3, while the PBS–treated eyes demonstrated stronger staining for MMP–9 in the anterior stroma at days 3 and 7 after injury. MMP–2 gene expression was decreased in the Tß4–treated corneas at 7 days but leukolysin (MMP–25, MT6–MMP) and MMP–14 showed no significant differences at any of the time points between the two groups. Tissue inhibitor of metalloproteinase (TIMP)–1 and –2 expression showed no significant changes between the two groups. Conclusions:4 promotes corneal wound healing, decreases gene expression of the PMN chemoattractant, KC, and PMN infiltration in a BALB/c mouse model of alkali injury. The modulated expression of key extracellular matrix remodeling molecules MMP–2 and –9 by Tß4 suggests a possible mechanism for its effects on corneal wound repair.

Keywords: extracellular matrix • wound healing • inflammation 
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