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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

Nicolas Taveau
  • Fonction : Auteur
Aurélie Cubizolle
  • Fonction : Auteur
Laurent Guillou
  • Fonction : Auteur
Nicolas Pinquier
  • Fonction : Auteur
Espérance Moine
  • Fonction : Auteur
David Cia
  • Fonction : Auteur
Vasiliki Kalatzis
  • Fonction : Auteur
Joseph Vercauteren
  • Fonction : Auteur
Thierry Durand
  • Fonction : Auteur
Céline Crauste
Philippe Brabet

Résumé

Abstract 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.

Dates et versions

hal-04256818 , version 1 (24-10-2023)

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Citer

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 (7), pp.1090-1101. ⟨10.1038/s12276-020-0460-7⟩. ⟨hal-04256818⟩

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