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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2015
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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. |
format | Online Article Text |
id | pubmed-4425572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
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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