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Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease
Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456345/ https://www.ncbi.nlm.nih.gov/pubmed/28575130 http://dx.doi.org/10.1371/journal.pone.0178753 |
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author | Beck, Susanne C. Feng, Yuxi Sothilingam, Vithiyanjali Garcia Garrido, Marina Tanimoto, Naoyuki Acar, Niyazi Shan, Shenliang Seebauer, Britta Berger, Wolfgang Hammes, Hans-Peter Seeliger, Mathias W. |
author_facet | Beck, Susanne C. Feng, Yuxi Sothilingam, Vithiyanjali Garcia Garrido, Marina Tanimoto, Naoyuki Acar, Niyazi Shan, Shenliang Seebauer, Britta Berger, Wolfgang Hammes, Hans-Peter Seeliger, Mathias W. |
author_sort | Beck, Susanne C. |
collection | PubMed |
description | Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects. |
format | Online Article Text |
id | pubmed-5456345 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-54563452017-06-12 Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease Beck, Susanne C. Feng, Yuxi Sothilingam, Vithiyanjali Garcia Garrido, Marina Tanimoto, Naoyuki Acar, Niyazi Shan, Shenliang Seebauer, Britta Berger, Wolfgang Hammes, Hans-Peter Seeliger, Mathias W. PLoS One Research Article Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects. Public Library of Science 2017-06-02 /pmc/articles/PMC5456345/ /pubmed/28575130 http://dx.doi.org/10.1371/journal.pone.0178753 Text en © 2017 Beck 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 Beck, Susanne C. Feng, Yuxi Sothilingam, Vithiyanjali Garcia Garrido, Marina Tanimoto, Naoyuki Acar, Niyazi Shan, Shenliang Seebauer, Britta Berger, Wolfgang Hammes, Hans-Peter Seeliger, Mathias W. Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease |
title | Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease |
title_full | Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease |
title_fullStr | Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease |
title_full_unstemmed | Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease |
title_short | Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease |
title_sort | long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of norrie disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456345/ https://www.ncbi.nlm.nih.gov/pubmed/28575130 http://dx.doi.org/10.1371/journal.pone.0178753 |
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