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Isopropyl-phloroglucinol-DHA protects outer retinal cells against lethal dose of all-trans-retinal.


ABSTRACT: All-trans-retinal (atRAL) is a highly reactive carbonyl specie, known for its reactivity on cellular phosphatidylethanolamine in photoreceptor. It is generated by photoisomerization of 11-cis-retinal chromophore linked to opsin by the Schiff's base reaction. In ABCA4-associated autosomal recessive Stargardt macular dystrophy, atRAL results in carbonyl and oxidative stress, which leads to bisretinoid A2E, accumulation in the retinal pigment epithelium (RPE). This A2E-accumulation presents as lipofuscin fluorescent pigment, and its photooxidation causes subsequent damage. Here we describe protection against a lethal dose of atRAL in both photoreceptors and RPE in primary cultures by a lipidic polyphenol derivative, an isopropyl-phloroglucinol linked to DHA, referred to as IP-DHA. Next, we addressed the cellular and molecular defence mechanisms in commonly used human ARPE-19 cells. We determined that both polyunsaturated fatty acid and isopropyl substituents bond to phloroglucinol are essential to confer the highest protection. IP-DHA responds rapidly against the toxicity of atRAL and its protective effect persists. This healthy effect of IP-DHA applies to the mitochondrial respiration. IP-DHA also rescues RPE cells subjected to the toxic effects of A2E after blue light exposure. Together, our findings suggest that the beneficial role of IP-DHA in retinal cells involves both anti-carbonyl and anti-oxidative capacities.

SUBMITTER: Cubizolle A 

PROVIDER: S-EPMC7205824 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Isopropyl-phloroglucinol-DHA protects outer retinal cells against lethal dose of all-trans-retinal.

Cubizolle Aurélie A   Cia David D   Moine Espérance E   Jacquemot Nathalie N   Guillou Laurent L   Rosell Mélissa M   Angebault-Prouteau Claire C   Lenaers Guy G   Meunier Isabelle I   Vercauteren Joseph J   Durand Thierry T   Crauste Céline C   Brabet Philippe P  

Journal of cellular and molecular medicine 20200325 9


All-trans-retinal (atRAL) is a highly reactive carbonyl specie, known for its reactivity on cellular phosphatidylethanolamine in photoreceptor. It is generated by photoisomerization of 11-cis-retinal chromophore linked to opsin by the Schiff's base reaction. In ABCA4-associated autosomal recessive Stargardt macular dystrophy, atRAL results in carbonyl and oxidative stress, which leads to bisretinoid A2E, accumulation in the retinal pigment epithelium (RPE). This A2E-accumulation presents as lipo  ...[more]

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