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Increased VEGF‐A promotes multiple distinct aging diseases of the eye through shared pathomechanisms
While increased VEGF‐A has been associated with neovascular age‐related macular degeneration (AMD), it is not known whether VEGF‐A may also promote other age‐related eye diseases. Here, we show that an increase in VEGF‐A is sufficient to cause multiple distinct common aging diseases of the eye, incl...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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John Wiley and Sons Inc.
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772957/ https://www.ncbi.nlm.nih.gov/pubmed/26912740 http://dx.doi.org/10.15252/emmm.201505613 |
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author | Marneros, Alexander G |
author_facet | Marneros, Alexander G |
author_sort | Marneros, Alexander G |
collection | PubMed |
description | While increased VEGF‐A has been associated with neovascular age‐related macular degeneration (AMD), it is not known whether VEGF‐A may also promote other age‐related eye diseases. Here, we show that an increase in VEGF‐A is sufficient to cause multiple distinct common aging diseases of the eye, including cataracts and both neovascular and non‐exudative AMD‐like pathologies. In the lens, increased VEGF‐A induces age‐related opacifications that are associated with ERK hyperactivation, increased oxidative damage, and higher expression of the NLRP3 inflammasome effector cytokine IL‐1β. Similarly, increased VEGF‐A induces oxidative stress and IL‐1β expression also in the retinal pigment epithelium (RPE). Targeting NLRP3 inflammasome components or Il1r1 strongly inhibited not only VEGF‐A‐induced cataract formation, but also both neovascular and non‐exudative AMD‐like pathologies. Moreover, increased VEGF‐A expression specifically in the RPE was sufficient to cause choroidal neovascularization (CNV) as in neovascular AMD, which could be inhibited by RPE‐specific inactivation of Flk1, while Tlr2 inactivation strongly reduced CNV. These findings suggest a shared pathogenic role of VEGF‐A‐induced and NLRP3 inflammasome‐mediated IL‐1β activation for multiple distinct ocular aging diseases. |
format | Online Article Text |
id | pubmed-4772957 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-47729572016-04-01 Increased VEGF‐A promotes multiple distinct aging diseases of the eye through shared pathomechanisms Marneros, Alexander G EMBO Mol Med Research Articles While increased VEGF‐A has been associated with neovascular age‐related macular degeneration (AMD), it is not known whether VEGF‐A may also promote other age‐related eye diseases. Here, we show that an increase in VEGF‐A is sufficient to cause multiple distinct common aging diseases of the eye, including cataracts and both neovascular and non‐exudative AMD‐like pathologies. In the lens, increased VEGF‐A induces age‐related opacifications that are associated with ERK hyperactivation, increased oxidative damage, and higher expression of the NLRP3 inflammasome effector cytokine IL‐1β. Similarly, increased VEGF‐A induces oxidative stress and IL‐1β expression also in the retinal pigment epithelium (RPE). Targeting NLRP3 inflammasome components or Il1r1 strongly inhibited not only VEGF‐A‐induced cataract formation, but also both neovascular and non‐exudative AMD‐like pathologies. Moreover, increased VEGF‐A expression specifically in the RPE was sufficient to cause choroidal neovascularization (CNV) as in neovascular AMD, which could be inhibited by RPE‐specific inactivation of Flk1, while Tlr2 inactivation strongly reduced CNV. These findings suggest a shared pathogenic role of VEGF‐A‐induced and NLRP3 inflammasome‐mediated IL‐1β activation for multiple distinct ocular aging diseases. John Wiley and Sons Inc. 2016-02-24 2016-03 /pmc/articles/PMC4772957/ /pubmed/26912740 http://dx.doi.org/10.15252/emmm.201505613 Text en © 2016 The Author. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Marneros, Alexander G Increased VEGF‐A promotes multiple distinct aging diseases of the eye through shared pathomechanisms |
title | Increased VEGF‐A promotes multiple distinct aging diseases of the eye through shared pathomechanisms |
title_full | Increased VEGF‐A promotes multiple distinct aging diseases of the eye through shared pathomechanisms |
title_fullStr | Increased VEGF‐A promotes multiple distinct aging diseases of the eye through shared pathomechanisms |
title_full_unstemmed | Increased VEGF‐A promotes multiple distinct aging diseases of the eye through shared pathomechanisms |
title_short | Increased VEGF‐A promotes multiple distinct aging diseases of the eye through shared pathomechanisms |
title_sort | increased vegf‐a promotes multiple distinct aging diseases of the eye through shared pathomechanisms |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772957/ https://www.ncbi.nlm.nih.gov/pubmed/26912740 http://dx.doi.org/10.15252/emmm.201505613 |
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