Calcium Dobesilate Inhibits the Alterations in Tight Junction Proteins and Leukocyte Adhesion to Retinal Endothelial Cells Induced by Diabetes

• DOI: 10.2337/db09-1421
• Publication Date: 2010-07-14T02:25:17Z
• Authors: Ermelindo C. Leal; João Martins; Paula Voabil; Joana Liberal; Carlo Chiavaroli; Jacques Bauer; José Cunha-Vaz; António F. Ambrósio
• Keywords: Occludin; Blood–retinal barrier; Evans Blue; Vascular permeability

OBJECTIVE Calcium dobesilate (CaD) has been used in the treatment of diabetic retinopathy last decades, but its mechanisms action are not elucidated. CaD is able to correct excessive vascular permeability retina patients and experimental diabetes. We investigated molecular cellular underlying protective effects against increase blood–retinal barrier (BRB) induced by RESEARCH DESIGN AND METHODS Wistar rats were divided into three groups: controls, streptozotocin-induced rats, treated with CaD. The BRB breakdown was evaluated using Evans blue. content or distribution tight junction proteins (occludin, claudin-5, zonula occluden-1 [ZO-1]), intercellular adhesion molecule-1 (ICAM-1), p38 mitogen-activated protein kinase (p38 MAPK) Western blotting immunohistochemistry. Leukocyte retinal vessels vitro. Oxidative stress detection oxidized carbonyls tyrosine nitration. NF-κB activation measured enzyme-linked immunosorbent assay. RESULTS Diabetes increased thickness. also decreased occludin claudin-5 levels altered ZO-1 vessels. These changes inhibited treatment. leukocyte endothelial cells ICAM-1 levels, diabetes elevated glucose. Moreover, oxidative MAPK caused CONCLUSIONS prevents diabetes, restoring organization decreasing likely involve inhibition activation, possibly through oxidative/nitrosative stress.