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Safety and angiogenic effects of systemic gene delivery of a modified erythropoietin

Erythropoietin (EPO) is critical for red blood cell production and is also an effective neuroprotective agent. However, it may also contribute to pathological angiogenesis. Here we investigate the angiogenic potential of EPO and a mutant form with attenuated erythropoietic activity, EPO-R76E, on pri...

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Autores principales: de Lucas Cerrillo, Ana, Bond, Wesley S., Rex, Tonia S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425572/
https://www.ncbi.nlm.nih.gov/pubmed/25716531
http://dx.doi.org/10.1038/gt.2015.12
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author de Lucas Cerrillo, Ana
Bond, Wesley S.
Rex, Tonia S.
author_facet de Lucas Cerrillo, Ana
Bond, Wesley S.
Rex, Tonia S.
author_sort de Lucas Cerrillo, Ana
collection PubMed
description Erythropoietin (EPO) is critical for red blood cell production and is also an effective neuroprotective agent. However, it may also contribute to pathological angiogenesis. Here we investigate the angiogenic potential of EPO and a mutant form with attenuated erythropoietic activity, EPO-R76E, on primary human retinal microvascular endothelial cells (HRMEC) and in the adult retina. Assays of death, proliferation, and tube-formation were performed on HRMECs exposed to EPO, EPO-R76E, or media alone. Postnatal day 9 wild-type mice were injected intramuscularly with adeno-associated virus vectors expressing either enhanced green fluorescent protein or EpoR76E. At 3 months, levels of EPO-R76E in the eye were quantified, and the health of the retinal vasculature was assessed by fluorescein angiography and isolectin immunolabeling. Immunohistochemistry, histology, and electroretinogram assessments were performed as measures of retinal health. Neither EPO nor EPO-R76E induced proliferation or tube-formation in HRMEC under the conditions used. EPO-R76E decreased HRMEC death in a dose-dependent manner. Long-term systemic gene delivery of EPO-R76E was safe in terms of retinal vasculature, histology, and the electroretinogram in vivo. Our results show that EPO-R76E can block HRMEC death, consistent with its role in erythropoiesis and neuroprotection. In addition, long-term gene delivery of EPO-R76E is safe in the adult retina.
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spelling pubmed-44255722015-11-01 Safety and angiogenic effects of systemic gene delivery of a modified erythropoietin de Lucas Cerrillo, Ana Bond, Wesley S. Rex, Tonia S. Gene Ther Article Erythropoietin (EPO) is critical for red blood cell production and is also an effective neuroprotective agent. However, it may also contribute to pathological angiogenesis. Here we investigate the angiogenic potential of EPO and a mutant form with attenuated erythropoietic activity, EPO-R76E, on primary human retinal microvascular endothelial cells (HRMEC) and in the adult retina. Assays of death, proliferation, and tube-formation were performed on HRMECs exposed to EPO, EPO-R76E, or media alone. Postnatal day 9 wild-type mice were injected intramuscularly with adeno-associated virus vectors expressing either enhanced green fluorescent protein or EpoR76E. At 3 months, levels of EPO-R76E in the eye were quantified, and the health of the retinal vasculature was assessed by fluorescein angiography and isolectin immunolabeling. Immunohistochemistry, histology, and electroretinogram assessments were performed as measures of retinal health. Neither EPO nor EPO-R76E induced proliferation or tube-formation in HRMEC under the conditions used. EPO-R76E decreased HRMEC death in a dose-dependent manner. Long-term systemic gene delivery of EPO-R76E was safe in terms of retinal vasculature, histology, and the electroretinogram in vivo. Our results show that EPO-R76E can block HRMEC death, consistent with its role in erythropoiesis and neuroprotection. In addition, long-term gene delivery of EPO-R76E is safe in the adult retina. 2015-02-26 2015-05 /pmc/articles/PMC4425572/ /pubmed/25716531 http://dx.doi.org/10.1038/gt.2015.12 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
de Lucas Cerrillo, Ana
Bond, Wesley S.
Rex, Tonia S.
Safety and angiogenic effects of systemic gene delivery of a modified erythropoietin
title Safety and angiogenic effects of systemic gene delivery of a modified erythropoietin
title_full Safety and angiogenic effects of systemic gene delivery of a modified erythropoietin
title_fullStr Safety and angiogenic effects of systemic gene delivery of a modified erythropoietin
title_full_unstemmed Safety and angiogenic effects of systemic gene delivery of a modified erythropoietin
title_short Safety and angiogenic effects of systemic gene delivery of a modified erythropoietin
title_sort safety and angiogenic effects of systemic gene delivery of a modified erythropoietin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425572/
https://www.ncbi.nlm.nih.gov/pubmed/25716531
http://dx.doi.org/10.1038/gt.2015.12
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