Calcium dobesilate decreases diabetes-induced retinal vessel leakage and leukocyte adhesion to retinal endothelial cells

Abstract

Event Abstract Back to Event Calcium dobesilate decreases diabetes-induced retinal vessel leakage and leukocyte adhesion to retinal endothelial cells Ermelindo C. Leal1, 2, 3*, Joao Martins1, 2, 3, Carlo Chiavaroli4, Jose Cunha-Vaz2 and Antonio F. Ambrosio1, 2, 3 1 University of Coimbra, Center of Ophthalmology and Vision Sciences, IBILI, Faculty of Medicine, Portugal 2 AIBILI, Portugal 3 University of Coimbra, Center for Neuroscience and Cell Biology, Portugal 4 Om Pharma, Switzerland The breakdown of blood-retinal barrier (BRB) is a hallmark of diabetic retinopathy. In animal models, retinal vessel leakage occurs early after diabetes induction and it is correlated with leukocyte adhesion to retinal endothelial cells. Calcium dobesilate (CaD) has been found to correct the excessive retinal vascular permeability in diabetic patients and experimental diabetes. We investigated the effect of CaD on the content and distribution of tight junction proteins in retinal vessels of diabetic rats, and on leukocyte adhesion to retinal endothelial cells. Diabetes (1 month duration) was induced in Wistar rats (8-10 weeks old) with a single streptozotocin injection (i.p., 65 mg/kg; type I diabetes model). The animals were divided into three groups (7- 8 animals/group): controls, diabetics, diabetics treated with CaD (100 mg/kg/day; orally given) during the last 10 days of diabetes. BRB breakdown was assessed using Evans blue. Tight junction proteins and ICAM-1 protein levels were evaluated by western blotting. The distribution of tight junction proteins in retinal vessels was assessed by immunocytochemistry. Leukocyte adhesion was evaluated in whole-mounted retinas and using an in vitro assay, where retinal endothelial cells (TRiBRB2 cell line) were exposed to elevated glucose (30 mM). Diabetes induced a 6.5-fold increase in BRB permeability and this effect was correlated with a decrease in occludin and claudin-5 protein levels in the retina (65.2 ± 7.6% and 63.2 ± 5.4% of the control, respectively). ZO-1 protein levels were unchanged, but the distribution of ZO-1, and occluding, was altered in retinal vessels of diabetic animals. In diabetic animals treated with CaD, the BRB permeability decreased, when compared to diabetic animals, to 2-fold of the control, and the content and distribution of tight junction proteins were similar to control. In addition, CaD completely inhibited the increase in ICAM-1 levels in the retina and retinal endothelial cells, induced by diabetes and high glucose, respectively, and reduced by 50% or completely prevented the increase in the adhesion of leukocytes to diabetic retinal vessels or to cultured endothelial cells exposed to high glucose, respectively. In conclusion, CaD is able to prevent the BRB breakdown induced by diabetes, by restoring the content and distribution of tight junction proteins in retinal vessels and also by decreasing the leukocyte adhesion to endothelial cells.Support: OM PHARMA, Switzerland Conference: 11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009. Presentation Type: Poster Presentation Topic: Barriers of the Brain Citation: Leal EC, Martins J, Chiavaroli C, Cunha-Vaz J and Ambrosio AF (2009). Calcium dobesilate decreases diabetes-induced retinal vessel leakage and leukocyte adhesion to retinal endothelial cells. Front. Neurosci. Conference Abstract: 11th Meeting of the Portuguese Society for Neuroscience. doi: 10.3389/conf.neuro.01.2009.11.025 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 06 Aug 2009; Published Online: 06 Aug 2009. * Correspondence: Ermelindo C Leal, University of Coimbra, Center of Ophthalmology and Vision Sciences, IBILI, Faculty of Medicine, Alicante, Portugal, ecleal@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Ermelindo C Leal Joao Martins Carlo Chiavaroli Jose Cunha-Vaz Antonio F Ambrosio Google Ermelindo C Leal Joao Martins Carlo Chiavaroli Jose Cunha-Vaz Antonio F Ambrosio Google Scholar Ermelindo C Leal Joao Martins Carlo Chiavaroli Jose Cunha-Vaz Antonio F Ambrosio PubMed Ermelindo C Leal Joao Martins Carlo Chiavaroli Jose Cunha-Vaz Antonio F Ambrosio Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.