Occurrence of birefringent retinal inclusions in cynomolgus monkeys after high doses of canthaxanthin.

摘要: Purpose. To reproduce and investigate in a primate animal model the phenomenon of red carotenoid canthaxanthin (/?,/5-carotene-4'4'-dione) to induce crystal-like retinal deposits as they have been observed ocular fundus humans after high intake (i.e., more than 30 mg/day). Methods. Groups four cynomolgus monkeys (Macaco, fascicularis) per gender dose were administered 5.4, 16.2, or 48.6 mg candiaxanthin/kg body weight daily by oral gavage for 2.5 years. Eight control animals received placebo. In vivo ophthalmoscopy was performed at intervals 3 months along with electroretinography 12 24 biomicroscopy just before killed. Retinal wholemounts frozen sections investigated postmortem polarization, bright field, differential interference contrast microscopy. preterminal plasma concentrations determined high-performance liquid chromatography (HPLC). Results. By vivo, no crystals other lightreflecting particles central paramacular retina. However, polarization microscopy all canthaxanthin-treated showed circular zone peripheral retina containing birefringent, polymorphous red, orange, white inclusions. The density these inclusions diminished within 1 8 mm posterior ora serrata. These located mainly inner layers, that is, nerve fiber layer ganglion cell layer, plexiform nuclear layer. Twelve yellow, golden birefringent die macula. Retinas placebo-treated free HPLC confirmed presence all-trans canthaxanthin, 4-OH-echinenone isozeaxanthin well, retinas can thaxan dim-treated animals. Neither nor histopathology indicated any adverse effects canthaxanthin-induced seen this study. Conclusions. A years led deposition layers and, some extent, monkeys. did not interfere morphology function. Invest Ophthalmol Vis Sci. 1997;38:741-752.