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Anti-Human VEGF Repebody Effectively Suppresses Choroidal Neovascularization and Vascular Leakage

Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness among people over the age of 60. Vascular endothelial growth factor (VEGF) plays a major role in pathological angiogenesis in AMD. Herein, we present the development of an anti- human VEGF repebody, which is a s...

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Autores principales: Hwang, Da-Eun, Ryou, Jeong-Hyun, Oh, Jong Rok, Han, Jung Woo, Park, Tae Kwann, Kim, Hak-Sung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807815/
https://www.ncbi.nlm.nih.gov/pubmed/27015541
http://dx.doi.org/10.1371/journal.pone.0152522
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author Hwang, Da-Eun
Ryou, Jeong-Hyun
Oh, Jong Rok
Han, Jung Woo
Park, Tae Kwann
Kim, Hak-Sung
author_facet Hwang, Da-Eun
Ryou, Jeong-Hyun
Oh, Jong Rok
Han, Jung Woo
Park, Tae Kwann
Kim, Hak-Sung
author_sort Hwang, Da-Eun
collection PubMed
description Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness among people over the age of 60. Vascular endothelial growth factor (VEGF) plays a major role in pathological angiogenesis in AMD. Herein, we present the development of an anti- human VEGF repebody, which is a small-sized protein binder consisting of leucine-rich repeat (LRR) modules. The anti-VEGF repebody selected through a phage-display was shown to have a high affinity and specificity for human VEGF. We demonstrate that this repebody effectively inhibits in vitro angiogenic cellular processes, such as proliferation and migration, by blocking the VEGF-mediated signaling pathway. The repebody was also shown to have a strong suppression effect on choroidal neovascularization (CNV) and vascular leakage in vivo. Our results indicate that the anti-VEGF repebody has a therapeutic potential for treating neovascular AMD as well as other VEGF-involved diseases including diabetic retinopathy and metastatic cancers.
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spelling pubmed-48078152016-04-05 Anti-Human VEGF Repebody Effectively Suppresses Choroidal Neovascularization and Vascular Leakage Hwang, Da-Eun Ryou, Jeong-Hyun Oh, Jong Rok Han, Jung Woo Park, Tae Kwann Kim, Hak-Sung PLoS One Research Article Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness among people over the age of 60. Vascular endothelial growth factor (VEGF) plays a major role in pathological angiogenesis in AMD. Herein, we present the development of an anti- human VEGF repebody, which is a small-sized protein binder consisting of leucine-rich repeat (LRR) modules. The anti-VEGF repebody selected through a phage-display was shown to have a high affinity and specificity for human VEGF. We demonstrate that this repebody effectively inhibits in vitro angiogenic cellular processes, such as proliferation and migration, by blocking the VEGF-mediated signaling pathway. The repebody was also shown to have a strong suppression effect on choroidal neovascularization (CNV) and vascular leakage in vivo. Our results indicate that the anti-VEGF repebody has a therapeutic potential for treating neovascular AMD as well as other VEGF-involved diseases including diabetic retinopathy and metastatic cancers. Public Library of Science 2016-03-25 /pmc/articles/PMC4807815/ /pubmed/27015541 http://dx.doi.org/10.1371/journal.pone.0152522 Text en © 2016 Hwang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hwang, Da-Eun
Ryou, Jeong-Hyun
Oh, Jong Rok
Han, Jung Woo
Park, Tae Kwann
Kim, Hak-Sung
Anti-Human VEGF Repebody Effectively Suppresses Choroidal Neovascularization and Vascular Leakage
title Anti-Human VEGF Repebody Effectively Suppresses Choroidal Neovascularization and Vascular Leakage
title_full Anti-Human VEGF Repebody Effectively Suppresses Choroidal Neovascularization and Vascular Leakage
title_fullStr Anti-Human VEGF Repebody Effectively Suppresses Choroidal Neovascularization and Vascular Leakage
title_full_unstemmed Anti-Human VEGF Repebody Effectively Suppresses Choroidal Neovascularization and Vascular Leakage
title_short Anti-Human VEGF Repebody Effectively Suppresses Choroidal Neovascularization and Vascular Leakage
title_sort anti-human vegf repebody effectively suppresses choroidal neovascularization and vascular leakage
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807815/
https://www.ncbi.nlm.nih.gov/pubmed/27015541
http://dx.doi.org/10.1371/journal.pone.0152522
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