Overexpression of Hemopexin in the Diabetic Eye: a New Pathogenic Candidate for Diabetic Macular Edema

IntroductIon. Case-control study and experimental study. PurPose. Hemopexin is a well-recognized permeability factor in the kidney but its potential role in blood-retinal-barrier (BRB) breakdown has not been explored. The main aims of this study were: 1) To determine hemopexin expression in the retina and its content in the vitreous fluid from diabetic patients with diabetic macular edema (DME) and non-diabetic patients; 2) To evaluate the effect of hemopexin on BRB permeability; 3) To determine whether dexamethasone prevents an eventual hemopexin-induced hyperpermeability. Methods. Biological material: 1) Retinas from 10 diabetic donors with non-proliferative retinopathy (NPDR) and from 10 non-diabetic donors. 2) Vitreous fluid from 14 patients with DME and 14 non-diabetic patients. Hemopexin and LRP1 mRNA levels were measured by quantitative RT-PCR and hemopexin concentrations by ELISA. The effect of hemopexin on permeability in culture was evaluated by fluorescein isothiocyanate dextran movements in APRE-19 cells and bovine retinal endothelial cells. The experiments were repeated in the presence of hemopexin neutralizing antibodies and dexamethasone. results. A higher expression of hemopexin was detected in the RPE from diabetic patients in comparison with non-diabetic controls. Intravitreal hemopexin concentration was higher in patients with DME than in non-diabetic subjects. Hemopexin significantly increased permeability in ARPE-19 cells which was prevented by both hemopexin neutralizing antibodies and dexamethasone. conclusIons. Hemopexin is overexpressed in the RPE of diabetic patients with DME and induces the breakdown of RPE cells in vitro. Dexamethasone was able to prevent hemopexin-induced hyperpermeability. Our results suggest that hemopexin can be considered a new pathogenic candidate for DME. DEVELOPMENT OF A NEW BLOOD-RETINAL BARRIER MODEL IN VITRO A. Van der Wijk1, J. Wisniewska-Kruk1, I. Klaassen1, R. O. Schlingemann1,2 1Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; 2Department of Clinical and Molecular Ophthalmogenetics, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Science (KNAW), Amsterdam, The Netherlands