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KMID : 0620920200520070006
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Experimental & Molecular Medicine
2020 Volume.52 No. 7 p.6 ~ p.6
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Preclinical pharmacology of a lipophenol in a mouse model of light-induced retinopathy
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Taveau Nicolas
Cubizolle Aurelie
Guillou Laurent
Pinquier Nicolas
Moine Esperance
Cia David
Kalatzis Vasiliki
Vercauteren Joseph
Durand Thierry
Crauste Celine
Brabet Philippe
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Abstract
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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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KEYWORD
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Biologics, Retina
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