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Regina Goralczyk, Felix M. Barker, Susanne Buser, Hans Liechti, Jochen Bausch; Dose Dependency of Canthaxanthin Crystals in Monkey Retina and Spatial Distribution of its Metabolites. Invest. Ophthalmol. Vis. Sci. 2000;41(6):1513-1522.
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purpose. To establish the threshold level of canthaxanthin crystals in the
retina of cynomolgus monkeys. To correlate the spatial distribution of
all-trans canthaxanthin and its metabolites with the grade
of crystals. methods. Monkeys were orally administered 0, 0.2, 0.6, 1.8, 5.4, 16.2, and 48.6
mg/kg body wt canthaxanthin daily for 2.5 to 3 years. A second group of
monkeys were administered 200 and 500 mg/kg body wt/d for 5 years.
Ophthalmoscopy, electroretinography (ERG), retina and carotenoid
analysis were performed as previously reported.
results. Crystals in the retina periphery were observed by ophthalmoscopy
preterminally only in the extreme high doses of 200 to 500 mg/kg body
wt/d. There were no adverse effects on visual functions as measured by
ERG. Crystals in the peripheral retina, and/or in the macula, were
detected microscopically in all canthaxanthin treated groups except at
the lowest dose of 0.2 mg/kg body wt/d. The grade of crystals increased
up to a dose of 16.2 mg/kg body wt/d. Dose-dependent increases in
canthaxanthin content also were noted in the retina, the liver, and in
plasma. All-trans canthaxanthin was the major compound
in the peripheral and paracentral retina of very highly dosed animals,
where its concentration correlated largely with the grade of
inclusions. In the macula, 4′-OH-echinenone was the dominant
canthaxanthin metabolite. conclusions. The grade of crystals in monkey retinas was dose dependent with a
threshold level at 0.6 mg canthaxanthin/kg body wt/d. It correlated in
the retinal periphery with the concentrations of
all-trans-canthaxanthin and in the macula with its
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