thymosin and Diabetic-Retinopathy

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.

Topics: Apoptosis; Corneal Diseases; Diabetic Retinopathy; Epithelial Cells; Eye Diseases; Humans; Inflammation; Ocular Physiological Phenomena; Thymosin; Wound Healing

To examine an association between thymosin β4 as potentially angioproliferative factor and proliferative diabetic retinopathy.. The clinical study part included 62 patients with proliferative diabetic retinopathy (PDR) (study group) and 24 patients with non-diabetic pre-retinal membranes (control group). All patients underwent pars plana vitrectomy. We examined the thymosin β4 concentration in vitreous and plasma; and the expression of thymosin β4, glial fibrillary acidic protein (GFAP) and CD31 (PECAM-1 or Platelet Endothelial Cell Adhesion Molecule) and the levels of thymosin β4 mRNA and vascular endothelial growth factor (VEGF) mRNA in the excised membranes. The experimental study part consisted of 24 Sprague--Dawley rats with streptozotocin-induced diabetes mellitus and 24 age-matched control animals without diabetes. We determined the mRNA concentrations of thymosin β4, VEGF and GFAP in the rat retinas.. In the clinical study part, the vitreal and plasma thymosin β4 concentrations were significantly higher in the study group than control group (p =0.04 and p=0.01, respectively), and were significantly (p=0.028) correlated with each other. Co-expression of thymosin β4 and CD31 was observed in the diabetic fibrovascular membranes. Thymosin β4 mRNA and VEGF mRNA levels were significantly (p<0.01) higher in diabetic membranes than in non-diabetic membranes. In the experimental study part, the diabetic retinas showed co-localization of thymosin β4 and GFAP. The mRNA levels of thymosin β4, VEGF and GFAP were significantly (p<0.01) higher in diabetic rats than in control animals.. Thymosin β4 was produced in intraocular fibrovascular membranes of patients with PDR and in rats with experimental diabetes mellitus. Thymosin β4 may play a role in diabetic retinal neovascularization.

Topics: Adult; Aged; Animals; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique; Gene Expression; Glial Fibrillary Acidic Protein; Humans; Male; Middle Aged; Rats; Rats, Sprague-Dawley; Retinal Neovascularization; Thymosin; Vascular Endothelial Growth Factor A; Vitreous Body