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J Cell Mol Med. 2016 Sep;20(9):1651-63. doi: 10.1111/jcmm.12857. Epub 2016 Apr 12.

Phloroglucinol protects retinal pigment epithelium and photoreceptor against all-trans-retinal-induced toxicity and inhibits A2E formation.

Author information

1
Laboratoire de Biophysique Neurosensorielle, UMR INSERM 1107 Facultés de Médecine et de Pharmacie, Clermont-Ferrand, France.
2
Institut des Neurosciences de Montpellier, INSERM U1051, Montpellier, France.
3
Université Montpellier, Montpellier, France.
4
Institut des Biomolecules Max Mousseron (IBMM), UMR5247-CNRS-UM ENSCM Faculté de Pharmacie, Montpellier, France.
5
Centre de référence des affections sensorielles génétiques, CHRU, Montpellier, France.

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 (atRAL) and are involved in bisretinoid formation by condensation of atRAL with phosphatidylethanolamine (carbonyl stress) in the photoreceptor and its transformation into lipofuscin bisretinoids (oxidative stress) in the retinal pigment epithelium (RPE). As atRAL 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 atRAL-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 atRAL-induced intracellular reactive oxygen species and free atRAL levels. Moreover, we show that phloroglucinol reacts with atRAL 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 atRAL 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.

KEYWORDS:

all-trans-retinal; bisretinoid A2E; chromene adduct; phloroglucinol; photoreceptor; retinal pigment epithelium

PMID:
27072643
PMCID:
PMC4988284
DOI:
10.1111/jcmm.12857
[Indexed for MEDLINE]
Free PMC Article

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