thymosin-beta(4) and Corneal-Injuries

Persistent corneal epithelial defects and inflammation within the central cornea can directly distort visual acuity and may lead to permanent visual loss. Therefore, treatments with agents that enhance corneal reepithelialization and regulate the inflammatory response without the deleterious side effects of currently used agents such as corticosteroids would result in improved clinical outcome and would represent a major advance in the field. Despite much progress in the areas of corneal wound healing research, clinically available pharmacological therapies that can promote repair and limit the visual complications from persistent corneal wounds are severely limited and remains a major deficiency in the field. Prior studies from our laboratory have demonstrated the potent wound healing and anti-inflammatory effects of thymosin beta4 (Tbeta(4); Tbeta4) in numerous models of corneal injury. We are studying the mechanisms by which Tbeta(4) suppresses inflammation and promotes repair. Herein, we discuss some of our new basic scientific directions that may lead to the use of Tbeta(4) as a novel corneal wound healing and anti-inflammatory therapy.

Topics: Adrenal Cortex Hormones; Animals; Corneal Diseases; Corneal Injuries; Eye Injuries; Forecasting; Inflammation; Mice; Thymosin; Wound Healing

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

Topics: Animals; Cell Movement; Clinical Trials as Topic; Corneal Injuries; Eye Injuries; Humans; Myocardial Infarction; Neoplasms; Neovascularization, Physiologic; Thymalfasin; Thymosin; 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