Expression of erythropoietin and its receptor in the human retina: a comparative study of diabetic and nondiabetic subjects.
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-1alpha and HIF-2alpha).


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-1alpha, and HIF-2alpha (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-1alpha and HIF-2alpha 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.
García-Ramírez
Marta
M
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas, Instituto de Salud Carlos III, Diabetes Research Unit, Institut de Recerca Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain.
Hernández
Cristina
C
Simó
Rafael
R
D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002102:Cadaver; D003920:Diabetes Mellitus / Q000235:genetics*; D004921:Erythropoietin / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000502:physiology; D018613:Microscopy, Confocal; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000502:physiology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics*; D017467:Receptors, Erythropoietin / Q000235:genetics*; D012016:Reference Values; D012160:Retina / Q000502:physiology* / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D004921:Erythropoietin; D005904:Glial Fibrillary Acidic Protein; D051793:Hypoxia-Inducible Factor 1; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D000099162:Endothelial PAS Domain-Containing Protein 1