Background: Diabetic macular edema (DME) is resulted from the retinal microvascular
leakage that accompanies the breakdown of blood-retinal barrier. Triamcinolone acetonide (TA) is a
therapeutic agent for DME, but since the detailed mechanism of action of TA is not known, part of
its action was examined.
Methods: In vitro model to enhance the permeability of human retinal microvascular endothelial
cells (HRMECs) was constructed by using DME-related cytokines such as vascular endothelial
growth factor (VEGF), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). The efficacy of
TA and anti-VEGF antibody against retinal permeability was evaluated. Furthermore, the localization
of ZO-1 in HRMECs was examined using immunofluorescence staining and the expression
level of tight junction proteins (ZO-1, Occludin, and Claudin-5) was examined using immunoblot.
Results: TA and anti-VEGF antibody showed inhibitory effects against VEGF-induced permeability
enhancement, and TA also inhibited the increase in permeability induced by TNF-α and IL-1β. In
addition to the inhibitory effects against cytokine-induced hyperpermeability, TA enhanced the
barrier function of HRMECs and reduced the vascular leakage. TA altered the localization of tight
junction proteins, but did not increase the upregulation of tight junction proteins. Moreover, the
enhancement of barrier function by TA was inhibited by 17-AAG (glucocorticoid receptor inhibitor).
Conclusion: It was suggested that TA reinforced the barrier function through the glucocorticoid
receptor. In this study, we found that TA suppressed the inflammation caused by VEGF, TNF-α and
IL-1β, and decreased the retinal vascular hyperpermeability.