Intraocular expression of thymosin β4 in proliferative diabetic retinopathy

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.