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

[摘要] Background:Our previous results showed that in retinas from streptozotocin (STZ)-induced diabetic rats there is an increased level of interleukin-1β (IL-1β ). This cytokine may be involved in the expression of the inducible isoform of the nitric oxide synthase (iNOS), with consequent synthesis of large amounts of NO and blood–retinal barrier (BRB) breakdown.Aims:The aim of this work was to examine whether the administration of cyclosporin-A (Cs-A) to STZinduced diabetic rats inhibits the synthesis of IL-1β and the expression of the inducible proteins, iNOS and cyclo-oxygenase-2 (COX-2) in retinal cells, and whether the activity of these proteins contribute to BRB breakdown.Methods:The level of IL-1β was evaluated by ELISA and the NO production by L-{3H}-citrulline formation. Expression of iNOS and COX-2 proteins was determined by two methods, western blot and immunohistochemistry. The permeability of the BRB was assessed by quantification of the vitreous protein.Results and discussion:Our results indicated that the levels of IL-1β 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 diabetic rats with Cs-A also significantly inhibited the expression of the inducible proteins, iNOS and COX2. The evaluation of the vitreous protein content revealed that Cs-A also reduces the BRB permeability. Taken together, these results suggest that the increased production of the inflammatory mediators, IL-1β and NO, in diabetes may affect the BRB permeability and therefore contribute to the development of diabetic retinopathy.

[学科分类] 生理学与病理学