Phloroglucinol protects retinal pigment epithelium and photoreceptor against all‐trans‐retinal–induced toxicity and inhibits A2E formation. Issue 9 (12th April 2016)

• Record Type: Journal Article
• Authors: Cia, David; Cubizolle, Aurélie; Crauste, Céline; Jacquemot, Nathalie; Guillou, Laurent; Vigor, Claire; Angebault, Claire; Hamel, Christian P.; Vercauteren, Joseph; Brabet, Philippe
• Is Part Of: Journal of cellular and molecular medicine. Volume 20:Issue 9(2016)
• Page Start: 1651
• Page End: 1663
• Publication Date: 2016-04-12
• Subjects: all‐trans‐retinal -- bisretinoid A2E -- chromene adduct -- phloroglucinol -- photoreceptor -- retinal pigment epithelium; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.12857
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: Among retinal macular diseases, the juvenile recessive Stargardt disease and the age‐related degenerative disease arise from carbonyl and oxidative stresses (COS). Both stresses originate from an accumulation of all‐ trans ‐retinal (a t RAL) and are involved in bisretinoid formation by condensation of a t RAL with phosphatidylethanolamine (carbonyl stress) in the photoreceptor and its transformation into lipofuscin bisretinoids (oxidative stress) in the retinal pigment epithelium (RPE). As a t RAL and bisretinoid accumulation contribute to RPE and photoreceptor cell death, our goal is to select powerful chemical inhibitors of COS. Here, we describe that phloroglucinol, a natural phenolic compound having anti‐COS properties, protects both rat RPE and mouse photoreceptor primary cultures from a t RAL‐induced cell death and reduces hydrogen peroxide (H2 O2 )‐induced damage in RPE in a dose‐dependent manner. Mechanistic analyses demonstrate that the protective effect encompasses decrease in a t RAL‐induced intracellular reactive oxygen species and free a t RAL levels. Moreover, we show that phloroglucinol reacts with a t RAL to form a chromene adduct which prevents bisretinoid A2E synthesis in vitro . Taken together, these data show that the protective effect of phloroglucinol correlates with its ability to trap a t RAL and to prevent its further transformation into deleterious bisretinoids. Phloroglucinol might be a good basis to develop efficient therapeutic derivatives in the treatment of retinal macular diseases.