PURPOSE: The neuroprotective effect of carbamylated erythropoietin (CEPO), an erythropoietin (EPO) derivative, in diabetic retinopathy (DR) has not been clearly verified. We conducted this study to investigate the potential neuroprotective role of CEPO in a streptozotocin-induced diabetic rat model. METHODS: Streptozotocin-induced diabetic rats and blank controls were treated with or without CEPO and EPO for 4 weeks. Retinal functional and histological changes were quantified by electroretinogram, light microscopy, and terminal dUTP nick end labeling assay. Gene and protein levels of colony-stimulating factor 2 receptor beta, low-affinity (CD131), EPO receptor (EPOR), THY1, glial fibrillary acidic protein (GFAP), and vascular endothelial growth factor (VEGF-A) in retinal tissues were determined by real-time PCR and western blotting, respectively. Vascular penetration was assessed by fluorescein retinal angiography. RESULTS: Diabetic rats had decreased retinal thickness, decreased ganglion cells, and increased retinal neuron apoptosis. CEPO increased CD131 and THY1 expression, while EPO increased EPOR expression. High glucose increased GFAP expression in the diabetic group, but both CEPO and EPO attenuated the trend for increase. CEPO downregulated VEGF-A expression. The amplitudes of b-wave and oscillatory potentials were decreased in the untreated diabetic group, whereas neither parameter decreased in diabetic rats after CEPO or EPO treatment. Vascular leakage and microaneurysms in the diabetic group were significantly improved following CEPO treatment. CONCLUSIONS: CEPO has similar anti-apoptotic effects to EPO in DR, but CEPO does not induce neovascularization. CEPO may exert neuroprotective effects via its receptor CD131.
PURPOSE: The neuroprotective effect of carbamylated erythropoietin (CEPO), an erythropoietin (EPO) derivative, in diabetic retinopathy (DR) has not been clearly verified. We conducted this study to investigate the potential neuroprotective role of CEPO in a streptozotocin-induced diabeticrat model. METHODS:Streptozotocin-induced diabeticrats and blank controls were treated with or without CEPO and EPO for 4 weeks. Retinal functional and histological changes were quantified by electroretinogram, light microscopy, and terminal dUTP nick end labeling assay. Gene and protein levels of colony-stimulating factor 2 receptor beta, low-affinity (CD131), EPO receptor (EPOR), THY1, glial fibrillary acidic protein (GFAP), and vascular endothelial growth factor (VEGF-A) in retinal tissues were determined by real-time PCR and western blotting, respectively. Vascular penetration was assessed by fluorescein retinal angiography. RESULTS:Diabeticrats had decreased retinal thickness, decreased ganglion cells, and increased retinal neuron apoptosis. CEPO increased CD131 and THY1 expression, while EPO increased EPOR expression. High glucose increased GFAP expression in the diabetic group, but both CEPO and EPO attenuated the trend for increase. CEPO downregulated VEGF-A expression. The amplitudes of b-wave and oscillatory potentials were decreased in the untreated diabetic group, whereas neither parameter decreased in diabeticrats after CEPO or EPO treatment. Vascular leakage and microaneurysms in the diabetic group were significantly improved following CEPO treatment. CONCLUSIONS: CEPO has similar anti-apoptotic effects to EPO in DR, but CEPO does not induce neovascularization. CEPO may exert neuroprotective effects via its receptor CD131.
Authors: Carolyn E King; Jennifer Rodger; Carole Bartlett; Tammy Esmaili; Sarah A Dunlop; Lyn D Beazley Journal: Exp Neurol Date: 2007-01-25 Impact factor: 5.330
Authors: Marcel Leist; Pietro Ghezzi; Giovanni Grasso; Roberto Bianchi; Pia Villa; Maddalena Fratelli; Costanza Savino; Marina Bianchi; Jacob Nielsen; Jens Gerwien; Pekka Kallunki; Anna Kirstine Larsen; Lone Helboe; Søren Christensen; Lars O Pedersen; Mette Nielsen; Lars Torup; Thomas Sager; Alessandra Sfacteria; Serhat Erbayraktar; Zubeyde Erbayraktar; Necati Gokmen; Osman Yilmaz; Carla Cerami-Hand; Qiao-Wen Xie; Thomas Coleman; Anthony Cerami; Michael Brines Journal: Science Date: 2004-07-09 Impact factor: 47.728
Authors: Anna K Junk; Antonios Mammis; Sean I Savitz; Manjeet Singh; Steven Roth; Samit Malhotra; Pearl S Rosenbaum; Anthony Cerami; Michael Brines; Daniel M Rosenbaum Journal: Proc Natl Acad Sci U S A Date: 2002-07-18 Impact factor: 11.205
Authors: Michael Brines; Giovanni Grasso; Fabio Fiordaliso; Alessandra Sfacteria; Pietro Ghezzi; Maddalena Fratelli; Roberto Latini; Qiao-Wen Xie; John Smart; Chiao-Ju Su-Rick; Eileen Pobre; Deborah Diaz; Daniel Gomez; Carla Hand; Thomas Coleman; Anthony Cerami Journal: Proc Natl Acad Sci U S A Date: 2004-09-29 Impact factor: 11.205
Authors: Colin A Bretz; Aaron B Simmons; Eric Kunz; Aniket Ramshekar; Carson Kennedy; Ivan Cardenas; M Elizabeth Hartnett Journal: Am J Pathol Date: 2020-02-21 Impact factor: 4.307
Authors: S L Shirley Ding; S N Leow; R Munisvaradass; E H Koh; M L C Bastion; K Y Then; S Kumar; P L Mok Journal: Eye (Lond) Date: 2016-06-10 Impact factor: 3.775