Thymosin-beta4 modulates corneal matrix metalloproteinase levels and polymorphonuclear cell infiltration after alkali injury

Invest Ophthalmol Vis Sci. 2005 Jul;46(7):2388-95. doi: 10.1167/iovs.04-1368.


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-beta4 (Taubeta4) 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 Tbeta4 or PBS twice daily. At various time points after injury (PI), corneas from the Tbeta4- versus the PBS-treated group were examined for polymorphonuclear leukocyte (PMN) infiltration, chemokine, and matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) expression.

Results: Tbeta4-treated corneas demonstrated improved corneal clarity at day 7 PI. Whereas Tbeta4 decreased corneal MMP-2 and -9 and MT6-MMP levels after alkali injury, no change in TIMP-1 and -2 expression was detected. Tbeta4 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: Tbeta4 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 Tbeta4 may be useful clinically to treat severe inflammation-mediated corneal injuries.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Burns, Chemical / drug therapy*
  • Burns, Chemical / enzymology
  • Chemokines / metabolism
  • Corneal Diseases / chemically induced
  • Corneal Diseases / drug therapy*
  • Corneal Diseases / enzymology
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Eye Burns / chemically induced*
  • Matrix Metalloproteinases / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Neutrophil Infiltration / drug effects*
  • Neutrophils / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium Hydroxide
  • Thymosin / therapeutic use*
  • Tissue Inhibitor of Metalloproteinases / metabolism
  • Wound Healing / drug effects


  • Chemokines
  • Tissue Inhibitor of Metalloproteinases
  • thymosin beta(4)
  • Sodium Hydroxide
  • Thymosin
  • Matrix Metalloproteinases