[HTML][HTML] Low-dose erythropoietin inhibits oxidative stress and early vascular changes in the experimental diabetic retina

Q Wang, F Pfister, A Dorn-Beineke, F vom Hagen, J Lin… - Diabetologia, 2010 - Springer
Q Wang, F Pfister, A Dorn-Beineke, F vom Hagen, J Lin, Y Feng, HP Hammes
Diabetologia, 2010Springer
Aims/hypothesis Diabetic retinopathy is the result of increased oxidative and nitrosative
stress induced by chronic hyperglycaemia, and affects the vasculature and the neuroglia.
Erythropoietin is a neuroprotective and an endothelial survival factor. We assessed the effect
of suberythropoietic epoetin delta doses on variables of oxidative stress in target tissues of
diabetic complications and on pericyte loss in the diabetic retina. Methods We administered
epoetin delta to streptozotocin-induced diabetic Wistar rats at doses of 384 IU/kg body …
Aims/hypothesis
Diabetic retinopathy is the result of increased oxidative and nitrosative stress induced by chronic hyperglycaemia, and affects the vasculature and the neuroglia. Erythropoietin is a neuroprotective and an endothelial survival factor. We assessed the effect of suberythropoietic epoetin delta doses on variables of oxidative stress in target tissues of diabetic complications and on pericyte loss in the diabetic retina.
Methods
We administered epoetin delta to streptozotocin-induced diabetic Wistar rats at doses of 384 IU/kg body weight once weekly or 128 IU/kg body weight three times a week. The treatment lasted for 3 months. Oxidative stress and formation of AGEs were assessed by immunoblotting, expression of Ang-2 (also known as Angpt2) by RT-PCR, activation of protein kinase B (AKT) and heat shock protein (HSP)-27 levels by immunofluorescence, and incipient retinal vascular changes by quantitative morphometry of retinal digest preparations.
Results
Diabetes increased variables of oxidative stress and nitrosative stress (N ε-carboxymethyl-lysine, nitrotyrosine and methylglyoxal-type AGEs) in retina, kidney and heart of diabetic rats. Epoetin delta reduced oxidative and nitrosative stress in all tissues, and AGEs in the retina. It also reduced increased retinal Ang-2 expression and pericyte loss, and ameliorated p-AKT and HSP-27 levels.
Conclusions/interpretation
Epoetin delta has antioxidative properties in organs affected by diabetes and may prevent incipient microvascular damage in the diabetic retina.
Springer