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PLoS One. 2016 Dec 16;11(12):e0167793. doi: 10.1371/journal.pone.0167793. eCollection 2016.

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

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Sorbonne Universités, UPMC Univ Paris, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, Paris, France.
Biophytis, Parc BIOCITECH, 102 Avenue Gaston Roussel, Romainville, France.
IRIS-Pharma, Les Nertières, Allée Hector Pintus, La Gaude, France.


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.

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Conflict of interest statement

A patent “Composition for the protection of retinal pigment epithelium“ covering the topic of this manuscript has been filed on April 30, 2015 (FR 15 53957) and is owned by Stanislas Veillet, René Lafont, José-Alain Sahel, Valérie Fontaine and Pierre-Paul Elena. PP Elena is chairman of the Board of Iris Pharma and is shareholder of the Society. R Lafont is founder, CSO and shareholder of Biophytis. S. Veillet is founder, CEO and shareholder of Biophytis. This does not alter our adherence to PLOS ONE policies on sharing data and materials. We have no restriction to share these data.

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