Thymosin -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 -4 (T-4) has multiple, seemingly diverse, cellular functions. In the cornea, as in other tissues, T-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 T-4 in numerous models of corneal injury. Recently, we demonstrated that T-4 suppresses the activation of the transcription factor, nuclear factor-kappa b (NF-B) in TNF-α-stimulated cells. TNF-α initiates cell signaling pathways that converge on the activation of NF-B, thus both are known mediators of the inflammatory process. These results have important clinical implications for the potential role of T-4 as a corneal anti-inflammatory and wound-healing agent.
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 -4 (T-4) has multiple, seemingly diverse, cellular functions. In the cornea, as in other tissues, T-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 T-4 in numerous models of corneal injury. Recently, we demonstrated that T-4 suppresses the activation of the transcription factor, nuclear factor-kappa b (NF-B) in TNF-α-stimulated cells. TNF-α initiates cell signaling pathways that converge on the activation of NF-B, thus both are known mediators of the inflammatory process. These results have important clinical implications for the potential role of T-4 as a corneal anti-inflammatory and wound-healing agent.
Keywords: apoptosis; cell migration; cornea; inflammation; thymosin -4; wound healing
Document Type: Research Article
Affiliations: 1: Departments of Ophthalmology and Anatomy/Cell Biology, Kresge Eye Institute, Wayne State University School of Medicine, Detroit, Michigan, USA 2: Department of Ophthalmology, Kresge Eye Institute, Detroit, Michigan, USA
Publication date:
- Access Key
- Free content
- Partial Free content
- New content
- Open access content
- Partial Open access content
- Subscribed content
- Partial Subscribed content
- Free trial content