Preclinical pharmacology of a lipophenol in a mouse model of light-induced retinopathy
Environmental light has deleterious effects on the outer retina in human retinopathies, such as ABCA4-related Stargardt’s disease and dry age-related macular degeneration. These effects involve carbonyl and oxidative stress, which contribute to retinal cell death and vision loss. Here, we used an al...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080701/ https://www.ncbi.nlm.nih.gov/pubmed/32641711 http://dx.doi.org/10.1038/s12276-020-0460-7 |
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author | Taveau, Nicolas Cubizolle, Aurélie Guillou, Laurent Pinquier, Nicolas Moine, Espérance Cia, David Kalatzis, Vasiliki Vercauteren, Joseph Durand, Thierry Crauste, Céline Brabet, Philippe |
author_facet | Taveau, Nicolas Cubizolle, Aurélie Guillou, Laurent Pinquier, Nicolas Moine, Espérance Cia, David Kalatzis, Vasiliki Vercauteren, Joseph Durand, Thierry Crauste, Céline Brabet, Philippe |
author_sort | Taveau, Nicolas |
collection | PubMed |
description | Environmental light has deleterious effects on the outer retina in human retinopathies, such as ABCA4-related Stargardt’s disease and dry age-related macular degeneration. These effects involve carbonyl and oxidative stress, which contribute to retinal cell death and vision loss. Here, we used an albino Abca4(−/−) mouse model, the outer retina of which shows susceptibility to acute photodamage, to test the protective efficacy of a new polyunsaturated fatty acid lipophenol derivative. Anatomical and functional analyses demonstrated that a single intravenous injection of isopropyl-phloroglucinol-DHA, termed IP-DHA, dose-dependently decreased light-induced photoreceptor degeneration and preserved visual sensitivity. This protective effect persisted for 3 months. IP-DHA did not affect the kinetics of the visual cycle in vivo or the activity of the RPE65 isomerase in vitro. Moreover, IP-DHA administered by oral gavage showed significant protection of photoreceptors against acute light damage. In conclusion, short-term tests in Abca4-deficient mice, following single-dose administration and light exposure, identify IP-DHA as a therapeutic agent for the prevention of retinal degeneration. |
format | Online Article Text |
id | pubmed-8080701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80807012021-04-29 Preclinical pharmacology of a lipophenol in a mouse model of light-induced retinopathy Taveau, Nicolas Cubizolle, Aurélie Guillou, Laurent Pinquier, Nicolas Moine, Espérance Cia, David Kalatzis, Vasiliki Vercauteren, Joseph Durand, Thierry Crauste, Céline Brabet, Philippe Exp Mol Med Article Environmental light has deleterious effects on the outer retina in human retinopathies, such as ABCA4-related Stargardt’s disease and dry age-related macular degeneration. These effects involve carbonyl and oxidative stress, which contribute to retinal cell death and vision loss. Here, we used an albino Abca4(−/−) mouse model, the outer retina of which shows susceptibility to acute photodamage, to test the protective efficacy of a new polyunsaturated fatty acid lipophenol derivative. Anatomical and functional analyses demonstrated that a single intravenous injection of isopropyl-phloroglucinol-DHA, termed IP-DHA, dose-dependently decreased light-induced photoreceptor degeneration and preserved visual sensitivity. This protective effect persisted for 3 months. IP-DHA did not affect the kinetics of the visual cycle in vivo or the activity of the RPE65 isomerase in vitro. Moreover, IP-DHA administered by oral gavage showed significant protection of photoreceptors against acute light damage. In conclusion, short-term tests in Abca4-deficient mice, following single-dose administration and light exposure, identify IP-DHA as a therapeutic agent for the prevention of retinal degeneration. Nature Publishing Group UK 2020-07-08 /pmc/articles/PMC8080701/ /pubmed/32641711 http://dx.doi.org/10.1038/s12276-020-0460-7 Text en © The Author(s) 2020 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Taveau, Nicolas Cubizolle, Aurélie Guillou, Laurent Pinquier, Nicolas Moine, Espérance Cia, David Kalatzis, Vasiliki Vercauteren, Joseph Durand, Thierry Crauste, Céline Brabet, Philippe Preclinical pharmacology of a lipophenol in a mouse model of light-induced retinopathy |
title | Preclinical pharmacology of a lipophenol in a mouse model of light-induced retinopathy |
title_full | Preclinical pharmacology of a lipophenol in a mouse model of light-induced retinopathy |
title_fullStr | Preclinical pharmacology of a lipophenol in a mouse model of light-induced retinopathy |
title_full_unstemmed | Preclinical pharmacology of a lipophenol in a mouse model of light-induced retinopathy |
title_short | Preclinical pharmacology of a lipophenol in a mouse model of light-induced retinopathy |
title_sort | preclinical pharmacology of a lipophenol in a mouse model of light-induced retinopathy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080701/ https://www.ncbi.nlm.nih.gov/pubmed/32641711 http://dx.doi.org/10.1038/s12276-020-0460-7 |
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