Effect of cyclosporin-A on the blood-retinal barrier permeability in streptozotocin-induced diabetes

Background: Our previous results showed that in retinas from streptozotocin (STZ)-induced diabetic rats there is an increased level of interleukin-1 b eta (IL-1 beta). This cytokine may be involved in the expression of the ind ucible isoform of the nitric oxide synthase (iNOS), with consequent synthes is of large amounts of NO and blood-retinal barrier (BRB) breakdown. Aims: The aim of this work was to examine whether the administration of cyc losporin-A (Cs-A) to STZ-induced diabetic rats inhibits the synthesis of IL -1 beta and the expression of the inducible proteins, iNOS and cyclo-oxygen ase-2 (COX-2) in retinal cells, and whether the activity of these proteins contribute to BRB breakdown. Methods: The level of IL-1 beta was evaluated by ELISA and the NO productio n by L-{H-3}-citrulline formation. Expression of iNOS and COX-2 proteins wa s determined by two methods, western blot and immunohistochemistry. The per meability of the BRB was assessed by quantification of the vitreous protein . Results and discussion: Our results indicated that the levels of IL-1 beta and NO in retinas from Cs-A-treated diabetic rats are significantly reduced , as compared to that in non-treated diabetic rats. The treatment of diabet ic rats with Cs-A also significantly inhibited the expression of the induci ble proteins, iNOS and COX-2. The evaluation of the vitreous protein conten t revealed that Cs-A also reduces the BRB permeability. Taken together, the se results suggest that the increased production of the inflammatory mediat ors, IL-1 beta and NO, in diabetes may affect the BRB permeability and ther efore contribute to the development of diabetic retinopathy.