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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 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-
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.