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...

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Autores principales: Taveau, Nicolas, Cubizolle, Aurélie, Guillou, Laurent, Pinquier, Nicolas, Moine, Espérance, Cia, David, Kalatzis, Vasiliki, Vercauteren, Joseph, Durand, Thierry, Crauste, Céline, Brabet, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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.
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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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