Shunsuke Imai, Tomohiro Otsuka, Akira Naito, Masamitsu Shimazawa* and Hideaki Hara Pages 232 - 241 ( 10 )
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.
Diabetic macular edema, retinal vascular permeability, inflammation, triamcinolone acetonide, anti-VEGF, tight junction, glucocorticoid receptor.
Sagami Research Laboratories, Wakamoto Pharmaceutical Co., Ltd, Kanagawa, Sagami Research Laboratories, Wakamoto Pharmaceutical Co., Ltd, Kanagawa, Sagami Research Laboratories, Wakamoto Pharmaceutical Co., Ltd, Kanagawa, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501- 1196, Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu