Expression of Erythropoietin and Its Receptor in the Human Retina

Expression of Erythropoietin and Its Receptor in the Human Retina A comparative study of diabetic and nondiabetic subjects Marta García-Ramírez , PHD , Cristina Hernández , MD, PHD and Rafael Simó , MD, PHD From the CIBERDEM (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas) (Instituto de Salud Carlos III) and Diabetes Research Unit, Institut de Recerca Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain Corresponding author: Dr. Rafael Simó, Diabetes Research Unit. Endocrinology Division, Hospital Universitari Vall d’Hebron, Pg. Vall d’Hebron 119-129, 08035 Barcelona, Spain. E-mail: rsimo{at}ir.vhebron.net Abstract OBJECTIVE —The purpose of this study was to evaluate erythropoietin (Epo) and Epo receptor (EpoR) expression in the retina and in vitreous fluid from diabetic and nondiabetic donors. To gain insight into the mechanisms responsible for the regulation of Epo production in the retina, we also assessed retinal expression of hypoxia-inducible factors (HIF-1α and HIF-2α). RESEARCH DESIGN AND METHODS —Eighteen postmortem eyes from 9 diabetic patients without clinically detectable retinopathy were compared with 18 eyes from 9 nondiabetic donors. mRNA of Epo, HIF-1α, and HIF-2α (quantitative RT-PCR) were measured separately in neuroretina and retinal pigment epithelium (RPE). Epo and EpoR were assessed in the retina (immunofluorescence by confocal laser microscopy) and in the vitreous fluid (radioimmunoassay and enzyme-linked immunosorbent assay, respectively). RESULTS —Epo and EpoR mRNAs were significantly higher in the RPE than in the neuroretina. Higher expression of Epo was detected in the retinas (both in the RPE and in the neuroretina) from diabetic donors. By contrast, EpoR expression was similar in both groups. We did not find any difference in HIF-1α and HIF-2α mRNA expression between diabetic and nondiabetic donors (both in RPE and neuroretina). Intravitreal Epo concentration was higher in diabetic donors than in nondiabetic control subjects. However, EpoR concentrations were similar in both groups. CONCLUSIONS —Epo overexpression is an early event in the retina of diabetic patients, and this is not associated with any change in EpoR. At this early stage, other factors apart from hypoxia seem to be more important in accounting for the Epo upregulation that exists in the diabetic retina. BBB, blood-brain barrier Epo, erythropoietin EpoR, erythropoietin receptor GFAP, glial fibr