Vitreous Levels of Erythropoietin in Diabetic Retinopathy

Abstract

Abstract: : Purpose: Diabetic retinopathy has traditionally been thought of as a vascular disease exclusively but recently, the question of whether it is also a neuronal disease has been raised. Erythropoietin (EPO) is demonstrated in models of retinal degeneration and clinical stroke to be both neuroprotective and haematopoietic. The objective of this study was to determine if EPO can be found in the human eye and to determine if it is upregulated in the vitreous of patients with diabetic retinopathy. An additional objective was to examine the relationship between vitreous VEGF–A and EPO concentrations. Methods: This was an observational case study evaluating vitreous EPO and VEGF–A concentrations in diabetic (n=19) and control (n=13) patients at the time of an elective pars plana vitrectomy for proliferative disease. Serum EPO and VEGF–A concentrations were also evaluated. Concentrations of EPO and VEGF–A were determined by ELISA (R&D Systems, Minneapolis, Minn.) and subjected to the Mann–Whitney rank sum test and the Pearson correlation. Results: Concentrations of vitreous EPO were significantly elevated in diabetic patients compared to controls (p < 0.0001). Vitreous EPO was significantly higher than serum EPO levels in diabetic patients. There was no significant difference in serum EPO among diabetic and control groups ( p < 0.0001). There was a significant correlation between EPO and VEGF–A concentration in vitreous fluid (r²=.61, p=0.0002) Conclusions: EPO can be found in the human eye and vitreous concentrations are elevated in patients with proliferative diabetic retinopathy, and are modestly correlated with vitreous concentrations of VEGF–A. Higher vitreous concentrations of EPO compared to serum EPO suggests a local production of EPO in the eye. Elevated EPO may reflect a neurodegenerative process in the pathogenesis of diabetic retinopathy, but awaits further analysis. We are currently looking for EPO in non–proliferative clinical specimens, and evaluating the role of EPO receptors in the NOD (non–obese diabetic) mouse retina.

Keywords: diabetic retinopathy • neuroprotection