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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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Detalles Bibliográficos
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
Descripción
Sumario: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.