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Article Dans Une Revue Experimental & Molecular Medicine Année : 2020

Preclinical pharmacology of a lipophenol in a mouse model of light-induced retinopathy

Résumé

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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Dates et versions

hal-03071488 , version 1 (16-12-2020)

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Nicolas Taveau, Aurélie Cubizolle, Laurent Guillou, Nicolas Pinquier, Espérance Moine, et al.. Preclinical pharmacology of a lipophenol in a mouse model of light-induced retinopathy. Experimental & Molecular Medicine, 2020, 52, pp.1090 - 1101. ⟨10.1038/s12276-020-0460-7⟩. ⟨hal-03071488⟩
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