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Oral Ursodeoxycholic Acid Crosses the Blood Retinal Barrier in Patients with Retinal Detachment and Protects Against Retinal Degeneration in an Ex Vivo Model
Rhegmatogenous retinal detachment (RD) is a threatening visual condition and a human disease model for retinal degenerations. Despite successful reattachment surgery, vision does not fully recover, due to subretinal fluid accumulation and subsequent photoreceptor cell death, through mechanisms that...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423962/ https://www.ncbi.nlm.nih.gov/pubmed/33537951 http://dx.doi.org/10.1007/s13311-021-01009-6 |
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author | Daruich, Alejandra Jaworski, Thara Henry, Hugues Zola, Marta Youale, Jenny Parenti, Léa Naud, Marie-Christine Delaunay, Kimberley Bertrand, Mathilde Berdugo, Marianne Kowalczuk, Laura Boatright, Jeffrey Picard, Emilie Behar-Cohen, Francine |
author_facet | Daruich, Alejandra Jaworski, Thara Henry, Hugues Zola, Marta Youale, Jenny Parenti, Léa Naud, Marie-Christine Delaunay, Kimberley Bertrand, Mathilde Berdugo, Marianne Kowalczuk, Laura Boatright, Jeffrey Picard, Emilie Behar-Cohen, Francine |
author_sort | Daruich, Alejandra |
collection | PubMed |
description | Rhegmatogenous retinal detachment (RD) is a threatening visual condition and a human disease model for retinal degenerations. Despite successful reattachment surgery, vision does not fully recover, due to subretinal fluid accumulation and subsequent photoreceptor cell death, through mechanisms that recapitulate those of retinal degenerative diseases. Hydrophilic bile acids are neuroprotective in animal models, but whether they can be used orally for retinal diseases is unknown. Ursodeoxycholic acid (UDCA) being approved for clinical use (e.g., in cholestasis), we have evaluated the ocular bioavailability of oral UDCA, administered to patients before RD surgery. The level of UDCA in ocular media correlated with the extent of blood retinal barrier disruption, evaluated by the extent of detachment and the albumin concentration in subretinal fluid. UDCA, at levels measured in ocular media, protected photoreceptors from apoptosis and necrosis in rat retinal explants, an ex vivo model of RD. The subretinal fluid from UDCA-treated patients, collected during surgery, significantly protected rat retinal explants from cell death, when compared to subretinal fluid from control patients. Pan-transcriptomic analysis of the retina showed that UDCA upregulated anti-apoptotic, anti-oxidant, and anti-inflammatory genes. Oral UDCA is a potential neuroprotective adjuvant therapy in RD and other retinal degenerative diseases and should be further evaluated in a clinical trial. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-021-01009-6. |
format | Online Article Text |
id | pubmed-8423962 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-84239622021-09-29 Oral Ursodeoxycholic Acid Crosses the Blood Retinal Barrier in Patients with Retinal Detachment and Protects Against Retinal Degeneration in an Ex Vivo Model Daruich, Alejandra Jaworski, Thara Henry, Hugues Zola, Marta Youale, Jenny Parenti, Léa Naud, Marie-Christine Delaunay, Kimberley Bertrand, Mathilde Berdugo, Marianne Kowalczuk, Laura Boatright, Jeffrey Picard, Emilie Behar-Cohen, Francine Neurotherapeutics Original Article Rhegmatogenous retinal detachment (RD) is a threatening visual condition and a human disease model for retinal degenerations. Despite successful reattachment surgery, vision does not fully recover, due to subretinal fluid accumulation and subsequent photoreceptor cell death, through mechanisms that recapitulate those of retinal degenerative diseases. Hydrophilic bile acids are neuroprotective in animal models, but whether they can be used orally for retinal diseases is unknown. Ursodeoxycholic acid (UDCA) being approved for clinical use (e.g., in cholestasis), we have evaluated the ocular bioavailability of oral UDCA, administered to patients before RD surgery. The level of UDCA in ocular media correlated with the extent of blood retinal barrier disruption, evaluated by the extent of detachment and the albumin concentration in subretinal fluid. UDCA, at levels measured in ocular media, protected photoreceptors from apoptosis and necrosis in rat retinal explants, an ex vivo model of RD. The subretinal fluid from UDCA-treated patients, collected during surgery, significantly protected rat retinal explants from cell death, when compared to subretinal fluid from control patients. Pan-transcriptomic analysis of the retina showed that UDCA upregulated anti-apoptotic, anti-oxidant, and anti-inflammatory genes. Oral UDCA is a potential neuroprotective adjuvant therapy in RD and other retinal degenerative diseases and should be further evaluated in a clinical trial. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-021-01009-6. Springer International Publishing 2021-02-03 2021-04 /pmc/articles/PMC8423962/ /pubmed/33537951 http://dx.doi.org/10.1007/s13311-021-01009-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Daruich, Alejandra Jaworski, Thara Henry, Hugues Zola, Marta Youale, Jenny Parenti, Léa Naud, Marie-Christine Delaunay, Kimberley Bertrand, Mathilde Berdugo, Marianne Kowalczuk, Laura Boatright, Jeffrey Picard, Emilie Behar-Cohen, Francine Oral Ursodeoxycholic Acid Crosses the Blood Retinal Barrier in Patients with Retinal Detachment and Protects Against Retinal Degeneration in an Ex Vivo Model |
title | Oral Ursodeoxycholic Acid Crosses the Blood Retinal Barrier in Patients with Retinal Detachment and Protects Against Retinal Degeneration in an Ex Vivo Model |
title_full | Oral Ursodeoxycholic Acid Crosses the Blood Retinal Barrier in Patients with Retinal Detachment and Protects Against Retinal Degeneration in an Ex Vivo Model |
title_fullStr | Oral Ursodeoxycholic Acid Crosses the Blood Retinal Barrier in Patients with Retinal Detachment and Protects Against Retinal Degeneration in an Ex Vivo Model |
title_full_unstemmed | Oral Ursodeoxycholic Acid Crosses the Blood Retinal Barrier in Patients with Retinal Detachment and Protects Against Retinal Degeneration in an Ex Vivo Model |
title_short | Oral Ursodeoxycholic Acid Crosses the Blood Retinal Barrier in Patients with Retinal Detachment and Protects Against Retinal Degeneration in an Ex Vivo Model |
title_sort | oral ursodeoxycholic acid crosses the blood retinal barrier in patients with retinal detachment and protects against retinal degeneration in an ex vivo model |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423962/ https://www.ncbi.nlm.nih.gov/pubmed/33537951 http://dx.doi.org/10.1007/s13311-021-01009-6 |
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