Erythropoietin Is Highly Elevated in Vitreous Fluid of Patients With Proliferative Diabetic Retinopathy

Abstract

Diabetic retinopathy is characterized by increased vascular permeability, ischemia, and neovascularization. Ischemia in the retina can induce neovascularization via induction of vascular endothelial growth factor (VEGF) expression by the transcription factor hypoxia-inducible factor-1 (1). Hypoxia is also the main stimulus for erythropoietin (EPO) gene expression. It has been reported that EPO may have not only erythropoietic (2) but also neuroprotective (3) and angiogenic (4) effects. EPO is expressed at a number of sites including kidney, liver, brain, uterus (5), and the adult mammalian retina, which also expresses EPO receptors (6). The aim of this study was to investigate whether EPO is elevated in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR) and whether vitreous EPO levels are related to systemic levels of EPO, anemia, or nephropathy. Vitreous fluid samples were obtained from 59 PDR patients and 16 macular hole patients at the start of the vitrectomy procedure. Concentrations of EPO in vitreous fluid and serum samples were measured by an enzyme-linked immunosorbent assay for EPO (Toyobouseki, Osaka, Japan). Concentrations of VEGF were measured by an enzyme-linked immunosorbent assay for human VEGF (R & D Systems, Minneapolis, MN). Protein in vitreous fluid was determined using the method of Bradford (Bio-Rad, Hercules, CA). The Mann-Whitney U test was used to compare intravitreous concentrations of protein, VEGF, …