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M. Neuringer, P. J. Francis, L. Renner, A. Weiss, B. G. Jeffrey; Atrophic Macular Degeneration in Rhesus Monkeys Deficient in Xanthophylls and n-3 Fatty Acids. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2785.
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Macaque monkeys can provide a uniquely valuable model for studying age-related macular disease because they possess a macula and commonly develop early to intermediate stages of age-related maculopathy. Furthermore their maculopathy shares common genetic risk factors with human age-related macular degeneration (AMD).1 However, monkeys almost never spontaneously develop the advanced atrophic or neovascular stages of AMD. Whether this lack of progression is due in part to dietary factors remains unknown, because standard diets of laboratory nonhuman primates, compared to typical Western human diets, are very low in fat and high in nutrients thought to be important for retinal health. Such nutrients include lutein and zeaxanthin, the xanthophylls that form macular pigment, and n-3 fatty acids.
From birth until 14-16 years of age, 19 rhesus monkeys were fed semipurified diets lacking lutein and zeaxanthin and therefore they had no macular pigment. Eight of these received a diet also deficient in n-3 fatty acids and known to reduce retinal levels of docosahexaenoic acid (22:6n-3) by 80%; the remaining 11 received adequate n-3 fatty acids. Retinal pathology was monitored by color fundus photography, fluorescein angiography and spectral-domain OCT.
Monkeys fed xanthophyll-free diets showed an increased incidence of drusen at early ages. Two animals, both in the n-3 deficient group, developed atrophic changes in the macula by 15-16 years of age (equivalent to 45-48 human years). Color photographs showed areas of RPE disruption with pigmentary changes, and coincident hyperfluorescent window defects were seen on angiography. SD-OCT showed RPE disruption and large deposits extending into the photoreceptor layer. In both cases, atrophy appeared in an arc at ~1 mm eccentricity to the fovea in the superior macula.
In a separate study, we found histological evidence of increased macular lipofuscin fluorescence in monkeys on the same long-term diets deficient in both xanthophylls and n-3 fatty acids, and the highest levels of lipofuscin were found at a similar eccentricity to the atrophy found here. Given that atrophic macular disease is an extremely rare occurrence in monkeys, its appearance at a relatively young age in monkeys deficient in xanthophylls and n-3 fatty acids supports the role of these nutrients as significant factors for the prevention of macular disease.1PJ Francis et al, Hum Mol Gen 17:2673-2680, 2008.
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