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Retinal pigment epithelium extracellular vesicles are potent inducers of age‐related macular degeneration disease phenotype in the outer retina
Age‐related macular degeneration (AMD) is a leading cause of blindness. Vision loss is caused by the retinal pigment epithelium (RPE) and photoreceptors atrophy and/or retinal and choroidal angiogenesis. Here we use AMD patient‐specific RPE cells with the Complement Factor H Y402H high‐risk polymorp...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772497/ https://www.ncbi.nlm.nih.gov/pubmed/36544284 http://dx.doi.org/10.1002/jev2.12295 |
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author | Kurzawa‐Akanbi, Marzena Whitfield, Phillip Burté, Florence Bertelli, Pietro Maria Pathak, Varun Doherty, Mary Hilgen, Birthe Gliaudelytė, Lina Platt, Mark Queen, Rachel Coxhead, Jonathan Porter, Andrew Öberg, Maria Fabrikova, Daniela Davey, Tracey Beh, Chia Shyan Georgiou, Maria Collin, Joseph Boczonadi, Veronika Härtlova, Anetta Taggart, Michael Al‐Aama, Jumana Korolchuk, Viktor I Morris, Christopher M Guduric‐Fuchs, Jasenka Steel, David H Medina, Reinhold J Armstrong, Lyle Lako, Majlinda |
author_facet | Kurzawa‐Akanbi, Marzena Whitfield, Phillip Burté, Florence Bertelli, Pietro Maria Pathak, Varun Doherty, Mary Hilgen, Birthe Gliaudelytė, Lina Platt, Mark Queen, Rachel Coxhead, Jonathan Porter, Andrew Öberg, Maria Fabrikova, Daniela Davey, Tracey Beh, Chia Shyan Georgiou, Maria Collin, Joseph Boczonadi, Veronika Härtlova, Anetta Taggart, Michael Al‐Aama, Jumana Korolchuk, Viktor I Morris, Christopher M Guduric‐Fuchs, Jasenka Steel, David H Medina, Reinhold J Armstrong, Lyle Lako, Majlinda |
author_sort | Kurzawa‐Akanbi, Marzena |
collection | PubMed |
description | Age‐related macular degeneration (AMD) is a leading cause of blindness. Vision loss is caused by the retinal pigment epithelium (RPE) and photoreceptors atrophy and/or retinal and choroidal angiogenesis. Here we use AMD patient‐specific RPE cells with the Complement Factor H Y402H high‐risk polymorphism to perform a comprehensive analysis of extracellular vesicles (EVs), their cargo and role in disease pathology. We show that AMD RPE is characterised by enhanced polarised EV secretion. Multi‐omics analyses demonstrate that AMD RPE EVs carry RNA, proteins and lipids, which mediate key AMD features including oxidative stress, cytoskeletal dysfunction, angiogenesis and drusen accumulation. Moreover, AMD RPE EVs induce amyloid fibril formation, revealing their role in drusen formation. We demonstrate that exposure of control RPE to AMD RPE apical EVs leads to the acquisition of AMD features such as stress vacuoles, cytoskeletal destabilization and abnormalities in the morphology of the nucleus. Retinal organoid treatment with apical AMD RPE EVs leads to disrupted neuroepithelium and the appearance of cytoprotective alpha B crystallin immunopositive cells, with some co‐expressing retinal progenitor cell markers Pax6/Vsx2, suggesting injury‐induced regenerative pathways activation. These findings indicate that AMD RPE EVs are potent inducers of AMD phenotype in the neighbouring RPE and retinal cells. |
format | Online Article Text |
id | pubmed-9772497 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97724972022-12-23 Retinal pigment epithelium extracellular vesicles are potent inducers of age‐related macular degeneration disease phenotype in the outer retina Kurzawa‐Akanbi, Marzena Whitfield, Phillip Burté, Florence Bertelli, Pietro Maria Pathak, Varun Doherty, Mary Hilgen, Birthe Gliaudelytė, Lina Platt, Mark Queen, Rachel Coxhead, Jonathan Porter, Andrew Öberg, Maria Fabrikova, Daniela Davey, Tracey Beh, Chia Shyan Georgiou, Maria Collin, Joseph Boczonadi, Veronika Härtlova, Anetta Taggart, Michael Al‐Aama, Jumana Korolchuk, Viktor I Morris, Christopher M Guduric‐Fuchs, Jasenka Steel, David H Medina, Reinhold J Armstrong, Lyle Lako, Majlinda J Extracell Vesicles Research Articles Age‐related macular degeneration (AMD) is a leading cause of blindness. Vision loss is caused by the retinal pigment epithelium (RPE) and photoreceptors atrophy and/or retinal and choroidal angiogenesis. Here we use AMD patient‐specific RPE cells with the Complement Factor H Y402H high‐risk polymorphism to perform a comprehensive analysis of extracellular vesicles (EVs), their cargo and role in disease pathology. We show that AMD RPE is characterised by enhanced polarised EV secretion. Multi‐omics analyses demonstrate that AMD RPE EVs carry RNA, proteins and lipids, which mediate key AMD features including oxidative stress, cytoskeletal dysfunction, angiogenesis and drusen accumulation. Moreover, AMD RPE EVs induce amyloid fibril formation, revealing their role in drusen formation. We demonstrate that exposure of control RPE to AMD RPE apical EVs leads to the acquisition of AMD features such as stress vacuoles, cytoskeletal destabilization and abnormalities in the morphology of the nucleus. Retinal organoid treatment with apical AMD RPE EVs leads to disrupted neuroepithelium and the appearance of cytoprotective alpha B crystallin immunopositive cells, with some co‐expressing retinal progenitor cell markers Pax6/Vsx2, suggesting injury‐induced regenerative pathways activation. These findings indicate that AMD RPE EVs are potent inducers of AMD phenotype in the neighbouring RPE and retinal cells. John Wiley and Sons Inc. 2022-12-21 2022-12 /pmc/articles/PMC9772497/ /pubmed/36544284 http://dx.doi.org/10.1002/jev2.12295 Text en © 2022 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Articles Kurzawa‐Akanbi, Marzena Whitfield, Phillip Burté, Florence Bertelli, Pietro Maria Pathak, Varun Doherty, Mary Hilgen, Birthe Gliaudelytė, Lina Platt, Mark Queen, Rachel Coxhead, Jonathan Porter, Andrew Öberg, Maria Fabrikova, Daniela Davey, Tracey Beh, Chia Shyan Georgiou, Maria Collin, Joseph Boczonadi, Veronika Härtlova, Anetta Taggart, Michael Al‐Aama, Jumana Korolchuk, Viktor I Morris, Christopher M Guduric‐Fuchs, Jasenka Steel, David H Medina, Reinhold J Armstrong, Lyle Lako, Majlinda Retinal pigment epithelium extracellular vesicles are potent inducers of age‐related macular degeneration disease phenotype in the outer retina |
title | Retinal pigment epithelium extracellular vesicles are potent inducers of age‐related macular degeneration disease phenotype in the outer retina |
title_full | Retinal pigment epithelium extracellular vesicles are potent inducers of age‐related macular degeneration disease phenotype in the outer retina |
title_fullStr | Retinal pigment epithelium extracellular vesicles are potent inducers of age‐related macular degeneration disease phenotype in the outer retina |
title_full_unstemmed | Retinal pigment epithelium extracellular vesicles are potent inducers of age‐related macular degeneration disease phenotype in the outer retina |
title_short | Retinal pigment epithelium extracellular vesicles are potent inducers of age‐related macular degeneration disease phenotype in the outer retina |
title_sort | retinal pigment epithelium extracellular vesicles are potent inducers of age‐related macular degeneration disease phenotype in the outer retina |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772497/ https://www.ncbi.nlm.nih.gov/pubmed/36544284 http://dx.doi.org/10.1002/jev2.12295 |
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