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

Nicolas Taveau (1) , Aurélie Cubizolle (1) , Laurent Guillou (1) , Nicolas Pinquier (1) , Espérance Moine (2) , David Cia , Vasiliki Kalatzis (1) , Joseph Vercauteren (2) , Thierry Durand (2) , Céline Crauste (2) , Philippe Brabet (1)

1 INM - Institut des Neurosciences de Montpellier
2 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]

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.

Mots clés: 1234567890():

Domaines: Sciences du Vivant [q-bio]

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⟩