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The retinal toxicity profile towards assemblies of Amyloid-β indicate the predominant pathophysiological activity of oligomeric species
Amyloid-β (Aβ), reported as a significant constituent of drusen, was implicated in the pathophysiology of age-related macular degeneration (AMD), yet the identity of the major pathogenic Aβ species in the retina has remained hitherto unclear. Here, we examined the in-vivo retinal impact of distinct...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708452/ https://www.ncbi.nlm.nih.gov/pubmed/33262378 http://dx.doi.org/10.1038/s41598-020-77712-9 |
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author | Naaman, Efrat Ya’ari, Sarah Itzkovich, Chen Safuri, Shadi Macsi, Flora Kellerman, Lior Mimouni, Michael Mann, Irit Gazit, Ehud Adler-Abramovich, Lihi Zayit-Soudry, Shiri |
author_facet | Naaman, Efrat Ya’ari, Sarah Itzkovich, Chen Safuri, Shadi Macsi, Flora Kellerman, Lior Mimouni, Michael Mann, Irit Gazit, Ehud Adler-Abramovich, Lihi Zayit-Soudry, Shiri |
author_sort | Naaman, Efrat |
collection | PubMed |
description | Amyloid-β (Aβ), reported as a significant constituent of drusen, was implicated in the pathophysiology of age-related macular degeneration (AMD), yet the identity of the major pathogenic Aβ species in the retina has remained hitherto unclear. Here, we examined the in-vivo retinal impact of distinct supramolecular assemblies of Aβ. Fibrillar (Aβ40, Aβ42) and oligomeric (Aβ42) preparations showed clear biophysical hallmarks of amyloid assemblies. Measures of retinal structure and function were studied longitudinally following intravitreal administration of the various Aβ assemblies in rats. Electroretinography (ERG) delineated differential retinal neurotoxicity of Aβ species. Oligomeric Aβ42 inflicted the major toxic effect, exerting diminished ERG responses through 30 days post injection. A lesser degree of retinal dysfunction was noted following treatment with fibrillar Aβ42, whereas no retinal compromise was recorded in response to Aβ40 fibrils. The toxic effect of Aβ42 architectures was further reflected by retinal glial response. Fluorescence labelling of Aβ42 species was used to detect their accumulation into the retinal tissue. These results provide conceptual evidence of the differential toxicity of particular Aβ species in-vivo, and promote the mechanistic understanding of their retinal pathogenicity. Stratifying the impact of pathological Aβ aggregation in the retina may merit further investigation to decipher the pathophysiological relevance of processes of molecular self-assembly in retinal disorders. |
format | Online Article Text |
id | pubmed-7708452 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-77084522020-12-02 The retinal toxicity profile towards assemblies of Amyloid-β indicate the predominant pathophysiological activity of oligomeric species Naaman, Efrat Ya’ari, Sarah Itzkovich, Chen Safuri, Shadi Macsi, Flora Kellerman, Lior Mimouni, Michael Mann, Irit Gazit, Ehud Adler-Abramovich, Lihi Zayit-Soudry, Shiri Sci Rep Article Amyloid-β (Aβ), reported as a significant constituent of drusen, was implicated in the pathophysiology of age-related macular degeneration (AMD), yet the identity of the major pathogenic Aβ species in the retina has remained hitherto unclear. Here, we examined the in-vivo retinal impact of distinct supramolecular assemblies of Aβ. Fibrillar (Aβ40, Aβ42) and oligomeric (Aβ42) preparations showed clear biophysical hallmarks of amyloid assemblies. Measures of retinal structure and function were studied longitudinally following intravitreal administration of the various Aβ assemblies in rats. Electroretinography (ERG) delineated differential retinal neurotoxicity of Aβ species. Oligomeric Aβ42 inflicted the major toxic effect, exerting diminished ERG responses through 30 days post injection. A lesser degree of retinal dysfunction was noted following treatment with fibrillar Aβ42, whereas no retinal compromise was recorded in response to Aβ40 fibrils. The toxic effect of Aβ42 architectures was further reflected by retinal glial response. Fluorescence labelling of Aβ42 species was used to detect their accumulation into the retinal tissue. These results provide conceptual evidence of the differential toxicity of particular Aβ species in-vivo, and promote the mechanistic understanding of their retinal pathogenicity. Stratifying the impact of pathological Aβ aggregation in the retina may merit further investigation to decipher the pathophysiological relevance of processes of molecular self-assembly in retinal disorders. Nature Publishing Group UK 2020-12-01 /pmc/articles/PMC7708452/ /pubmed/33262378 http://dx.doi.org/10.1038/s41598-020-77712-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Naaman, Efrat Ya’ari, Sarah Itzkovich, Chen Safuri, Shadi Macsi, Flora Kellerman, Lior Mimouni, Michael Mann, Irit Gazit, Ehud Adler-Abramovich, Lihi Zayit-Soudry, Shiri The retinal toxicity profile towards assemblies of Amyloid-β indicate the predominant pathophysiological activity of oligomeric species |
title | The retinal toxicity profile towards assemblies of Amyloid-β indicate the predominant pathophysiological activity of oligomeric species |
title_full | The retinal toxicity profile towards assemblies of Amyloid-β indicate the predominant pathophysiological activity of oligomeric species |
title_fullStr | The retinal toxicity profile towards assemblies of Amyloid-β indicate the predominant pathophysiological activity of oligomeric species |
title_full_unstemmed | The retinal toxicity profile towards assemblies of Amyloid-β indicate the predominant pathophysiological activity of oligomeric species |
title_short | The retinal toxicity profile towards assemblies of Amyloid-β indicate the predominant pathophysiological activity of oligomeric species |
title_sort | retinal toxicity profile towards assemblies of amyloid-β indicate the predominant pathophysiological activity of oligomeric species |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708452/ https://www.ncbi.nlm.nih.gov/pubmed/33262378 http://dx.doi.org/10.1038/s41598-020-77712-9 |
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