Thymosin beta-4 and the eye: I can see clearly now the pain is gone

Abstract

The cornea epithelium responds to injury by synthesizing several cytokines, growth factors, and tissue remodeling molecules. Proinflammatory cytokines have been implicated in the inflammation that follows corneal epithelial injury and cytokine-mediated processes play a significant role in corneal epithelial wound healing. Poorly regulated corneal inflammatory reactions that occur after injury can retard healing. In turn, persistent corneal epithelial defects and inflammation may lead to ocular morbidity and 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. Evidence is mounting to support the idea that thymosin beta-4 (Tbeta-4) has multiple, seemingly diverse, cellular functions. In the cornea, as in other tissues, Tbeta-4 promotes cell migration and wound healing, has anti-inflammatory properties, and suppresses apoptosis. Prior studies from our laboratory have demonstrated the potent wound healing and anti-inflammatory effects of Tbeta-4 in numerous models of corneal injury. Recently, we demonstrated that Tbeta-4 suppresses the activation of the transcription factor, nuclear factor-kappa b (NF-kappaB) in TNF-alpha-stimulated cells. TNF-alpha initiates cell signaling pathways that converge on the activation of NF-kappaB, thus both are known mediators of the inflammatory process. These results have important clinical implications for the potential role of Tbeta-4 as a corneal anti-inflammatory and wound-healing agent.