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Developmental regression of hyaloid vasculature is triggered by neurons
Vascular development involves not only vascular growth, but also regression of transient or unnecessary vessels. Hyaloid vasculature is the temporary circulatory system in fetal eyes, which spontaneously degenerates when the retinal blood vessels start to grow. Failure of the hyaloid vessels to regr...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925022/ https://www.ncbi.nlm.nih.gov/pubmed/27325890 http://dx.doi.org/10.1084/jem.20151966 |
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author | Yoshikawa, Yusuke Yamada, Toru Tai-Nagara, Ikue Okabe, Keisuke Kitagawa, Yuko Ema, Masatsugu Kubota, Yoshiaki |
author_facet | Yoshikawa, Yusuke Yamada, Toru Tai-Nagara, Ikue Okabe, Keisuke Kitagawa, Yuko Ema, Masatsugu Kubota, Yoshiaki |
author_sort | Yoshikawa, Yusuke |
collection | PubMed |
description | Vascular development involves not only vascular growth, but also regression of transient or unnecessary vessels. Hyaloid vasculature is the temporary circulatory system in fetal eyes, which spontaneously degenerates when the retinal blood vessels start to grow. Failure of the hyaloid vessels to regress leads to disease in humans, persistent hyperplastic primary vitreous, which causes severe intraocular hemorrhage and impairs visual function. However, the mechanism underlying the endogenous program that mediates spontaneous regression of the hyaloid vessels is not well understood. In this study, we identify a robust switch triggering this program directed by neurons in mice. Marked up-regulation of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) occurs in retinal neurons just after birth via distal-multipotent-mesodermal enhancer, a hemangioblast-specific enhancer of VEGFR2. Genetic deletion of neuronal VEGFR2 interrupts this program, resulting in massive hyaloid vessels that persist even during late postnatal days. This abnormality is caused by excessive VEGF proteins in the vitreous cavity as a result of impairment in the neuronal sequestration of VEGF. Collectively, our data indicate that neurons trigger transition from the fetal to the postnatal circulatory systems in the retina. |
format | Online Article Text |
id | pubmed-4925022 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-49250222016-12-27 Developmental regression of hyaloid vasculature is triggered by neurons Yoshikawa, Yusuke Yamada, Toru Tai-Nagara, Ikue Okabe, Keisuke Kitagawa, Yuko Ema, Masatsugu Kubota, Yoshiaki J Exp Med Research Articles Vascular development involves not only vascular growth, but also regression of transient or unnecessary vessels. Hyaloid vasculature is the temporary circulatory system in fetal eyes, which spontaneously degenerates when the retinal blood vessels start to grow. Failure of the hyaloid vessels to regress leads to disease in humans, persistent hyperplastic primary vitreous, which causes severe intraocular hemorrhage and impairs visual function. However, the mechanism underlying the endogenous program that mediates spontaneous regression of the hyaloid vessels is not well understood. In this study, we identify a robust switch triggering this program directed by neurons in mice. Marked up-regulation of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) occurs in retinal neurons just after birth via distal-multipotent-mesodermal enhancer, a hemangioblast-specific enhancer of VEGFR2. Genetic deletion of neuronal VEGFR2 interrupts this program, resulting in massive hyaloid vessels that persist even during late postnatal days. This abnormality is caused by excessive VEGF proteins in the vitreous cavity as a result of impairment in the neuronal sequestration of VEGF. Collectively, our data indicate that neurons trigger transition from the fetal to the postnatal circulatory systems in the retina. The Rockefeller University Press 2016-06-27 /pmc/articles/PMC4925022/ /pubmed/27325890 http://dx.doi.org/10.1084/jem.20151966 Text en © 2016 Yoshikawa et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Yoshikawa, Yusuke Yamada, Toru Tai-Nagara, Ikue Okabe, Keisuke Kitagawa, Yuko Ema, Masatsugu Kubota, Yoshiaki Developmental regression of hyaloid vasculature is triggered by neurons |
title | Developmental regression of hyaloid vasculature is triggered by neurons |
title_full | Developmental regression of hyaloid vasculature is triggered by neurons |
title_fullStr | Developmental regression of hyaloid vasculature is triggered by neurons |
title_full_unstemmed | Developmental regression of hyaloid vasculature is triggered by neurons |
title_short | Developmental regression of hyaloid vasculature is triggered by neurons |
title_sort | developmental regression of hyaloid vasculature is triggered by neurons |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925022/ https://www.ncbi.nlm.nih.gov/pubmed/27325890 http://dx.doi.org/10.1084/jem.20151966 |
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