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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
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.
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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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