García-Ramírez Marta, Hernández Cristina, Simó Rafael
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.
Diabetes Care. 2008 Jun;31(6):1189-94. doi: 10.2337/dc07-2075. Epub 2008 Mar 10.
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).
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).
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.
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.
本研究旨在评估促红细胞生成素（Epo）和促红细胞生成素受体（EpoR）在糖尿病和非糖尿病供体的视网膜及玻璃体液中的表达情况。为深入了解视网膜中Epo产生的调控机制，我们还评估了缺氧诱导因子（HIF-1α和HIF-2α）的视网膜表达。
将9例无临床可检测视网膜病变的糖尿病患者的18只死后眼睛与9例非糖尿病供体的18只眼睛进行比较。分别在神经视网膜和视网膜色素上皮（RPE）中测量Epo、HIF-1α和HIF-2α的mRNA（定量逆转录聚合酶链反应）。通过共聚焦激光显微镜免疫荧光法评估视网膜中的Epo和EpoR，分别采用放射免疫分析法和酶联免疫吸附测定法评估玻璃体液中的Epo和EpoR。
RPE中Epo和EpoR的mRNA显著高于神经视网膜。在糖尿病供体的视网膜（RPE和神经视网膜）中检测到更高的Epo表达。相比之下，两组中EpoR的表达相似。我们未发现糖尿病和非糖尿病供体（RPE和神经视网膜）之间HIF-1α和HIF-2α mRNA表达有任何差异。糖尿病供体玻璃体内的Epo浓度高于非糖尿病对照受试者。然而，两组中EpoR的浓度相似。
Epo过表达是糖尿病患者视网膜的早期事件，且这与EpoR的任何变化无关。在这个早期阶段，除缺氧外的其他因素似乎在解释糖尿病视网膜中存在的Epo上调方面更为重要。
