EXPRESSION OF ERYTHROPOIETIN AND ITS RECEPTOR IN THE HUMAN RETINA. A comparative study of diabetic and non-diabetic subjects

Abstract

Objective To evaluate Epo and Epo receptor (EpoR) expression in the retina and in vitreous fluid from diabetic and non-diabetic donors. In order 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 non-diabetic donors. mRNA of Epo, HIF-1α and HIF-2α (Q-RT-PCR) were measured separately in neuroretina and retinal pigment epithelium (RPE). Epo and EpoR were assessed in the retina (immunoflurescence by confocal laser microscopy) and in the vitreous fluid (RIA and ELISA, respectively).

Results Epo and EpoR mRNAs were significantly higher in RPE than in the neuroretina. A 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 non-diabetic donors (both in RPE and neuroretina). Intravitreal Epo concentration was higher in diabetic donors than in non-diabetic controls. 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 up-regulation that exists in the diabetic retina.