thymosin-beta(4) and Burns--Chemical

Corneal alkali burns are a severe disease and commonly encountered in the emergent clinic. A rapid medical treatment for the burn is very important. Gly-thymosin β. Rabbit alkali burns were induced with NaOH-contained filter paper. Phosphate-buffered solutions at pH 7.0, Gly-Tβ. Gly-Tβ

Topics: Administration, Topical; Alkalies; Animals; Burns, Chemical; Corneal Injuries; Corneal Neovascularization; Disease Models, Animal; Epithelium, Corneal; Eye Burns; Hydrogels; Ophthalmic Solutions; Rabbits; Thymosin

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.. 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.. 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.. 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.

Topics: Animals; Burns, Chemical; Chemokines; Corneal Diseases; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Eye Burns; Matrix Metalloproteinases; Mice; Mice, Inbred BALB C; Neutrophil Infiltration; Neutrophils; Reverse Transcriptase Polymerase Chain Reaction; Sodium Hydroxide; Thymosin; Tissue Inhibitor of Metalloproteinases; Wound Healing

Previously, thymosin beta 4 (Tbeta(4)) was found to promote wound healing in full thickness skin wounds and heptanol debrided corneas. Here, the effect of Tbeta(4) was examined treatment on corneal wound healing and inflammation in vivo after alkali injury, a more severe wound of the eye. Corneas from 129 Sv mice were chemically burned with a 2 mm disc soaked in 1 N NaOH for 30 sec. Eyes were irrigated copiously with phosphate buffered saline (PBS) and then treated topically with either Tbeta(4) (5 microg/5 microl PBS) or 5 microl PBS twice daily. Animals were killed, the eyes were enucleated, fixed and embedded in plastic resin or prepared for mRNA analysis. Mouse corneas topically treated with 5 microg of Tbeta(4) twice daily after alkali injury demonstrated accelerated re-epithelialization at all time points and decreased polymorphonuclear leukocyte (PMN) infiltration at 7 days post injury (p.i.) when compared to PBS-treated controls. mRNA transcript levels were decreased several fold for interleukin (IL)-lbeta, and the chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, MIP-2 and monocyte chemoattractant protein (MCP)-1 from 1 to 7 days after injury in the Tbeta(4)- vs. PBS-treated corneas. Thus, Tbeta(4) may provide a new clinical treatment for severe traumatic corneal wound disorders by promoting rapid corneal wound healing and decreasing both PMN infiltration and inflammatory cytokine and chemokine mRNA levels.

Topics: Administration, Topical; Alkalies; Animals; Anti-Inflammatory Agents; Burns, Chemical; Chemokine CCL2; Chemokine CCL3; Chemokine CCL4; Chemokine CXCL2; Chemokines; Cornea; Corneal Injuries; Eye Burns; Interleukin-1; Macrophage Inflammatory Proteins; Mice; Mice, Inbred Strains; Microscopy, Electron; Receptors, Interleukin-1; RNA, Messenger; Thymosin; Time Factors; Wound Healing