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Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo

Fontaine, V; Monteiro, E; Brazhnikova, E; Lesage, L; Balducci, C; Guibout, L; Feraille, L; ... Lafont, R; + view all (2016) Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo. PLoS One , 11 (12) , Article e0167793. 10.1371/journal.pone.0167793. Green open access

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Abstract

The accumulation of N-retinylidene-N-retinylethanolamine (A2E, a toxic by-product of the visual pigment cycle) in the retinal pigment epithelium (RPE) is a major cause of visual impairment in the elderly. Photooxidation of A2E results in retinal pigment epithelium degeneration followed by that of associated photoreceptors. Present treatments rely on nutrient supplementation with antioxidants. 9'-cis-Norbixin (a natural diapocarotenoid, 97% purity) was prepared from Bixa orellana seeds. It was first evaluated in primary cultures of porcine retinal pigment epithelium cells challenged with A2E and illuminated with blue light, and it provided an improved photo-protection as compared with lutein or zeaxanthin. In Abca4-/- Rdh8-/- mice (a model of dry AMD), intravitreally-injected norbixin maintained the electroretinogram and protected photoreceptors against light damage. In a standard rat blue-light model of photodamage, norbixin was at least equally as active as phenyl-N-tert-butylnitrone, a free radical spin-trap. Chronic experiments performed with Abca4-/- Rdh8-/- mice treated orally for 3 months with norbixin showed a reduced A2E accumulation in the retina. Norbixin appears promising for developing an oral treatment of macular degeneration. A drug candidate (BIO201) with 9'-cis-norbixin as the active principle ingredient is under development, and its potential will be assessed in a forthcoming clinical trial.

Type: Article
Title: Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0167793
Publisher version: https://doi.org/10.1371/journal.pone.0167793
Language: English
Additional information: Copyright: © 2016 Fontaine et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: ATP-Binding Cassette Transporters, Alcohol Oxidoreductases, Animals, Bixaceae, Carotenoids, Cells, Cultured, Disease Models, Animal, In Vitro Techniques, Intravitreal Injections, Macular Degeneration, Mice, Mice, Knockout, Photoreceptor Cells, Vertebrate, Plant Extracts, Rats, Retinal Pigment Epithelium, Retinoids, Swine
URI: http://discovery.ucl.ac.uk/id/eprint/10054210
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