Intervention With an Erythropoietin-Derived Peptide Protects Against Neuroglial and Vascular Degeneration During Diabetic Retinopathy

• DOI: 10.2337/db11-0026
• Publication Date: 2011-09-13T06:46:45Z
• Authors: Carmel M. McVicar; Ross Hamilton; Liza M. Colhoun; Tom A. Gardiner; Michael Brines; Anthony Cerami; Alan W. Stitt
• Keywords: Proinflammatory cytokine

Erythropoietin (EPO) may be protective for early stage diabetic retinopathy, although there are concerns that it could exacerbate retinal angiogenesis and thrombosis. A peptide based on the EPO helix-B domain (helix B-surface [pHBSP]) is nonerythrogenic but retains tissue-protective properties, this study evaluates its therapeutic potential in retinopathy.After 6 months of streptozotocin-induced diabetes, rats (n = 12) age-matched nondiabetic controls were evenly split into pHBSP scrambled groups injected daily (10 μg/kg per day) 1 month. The retina was investigated glial dysfunction, microglial activation, neuronal DNA damage. vasculature dual stained with isolectin collagen IV. Retinal cytokine expression quantified using real-time RT-PCR. In parallel, oxygen-induced retinopathy (OIR) used to evaluate effects ischemia neovascularization (1-30 or control peptide).pHBSP treatment did not alter hematocrit. retina, Müller fibrillary acidic protein increased when compared controls, significantly reduced stress-related response (P < 0.001). CD11b+ microglia proinflammatory cytokines elevated responses, some these responses attenuated by 0.01-0.001). diabetes-linked damage as determined 8-hydroxydeoxyguanosine transferase-mediated dUTP nick-end labeling positivity also prevented acellular capillary formation 0.05). OIR, had no effect preretinal at any dose.Treatment an EPO-derived after diabetes fully established can protect against neuroglial vascular degenerative pathology without altering hematocrit exacerbating neovascularization. These findings have implications disorders such retinopathy.