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Laurie Renner, Sawan Hurst, Trevor McGill, Alison Weiss, Tim Stout, David Wilson, Martha Neuringer; Progression of Atrophic Macular Degeneration in Rhesus Monkeys Deficient in Lutein/Zeaxanthin and Omega-3 Fatty Acids. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4110.
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: Macaque monkeys possess a macula and commonly develop age-related maculopathy that shares common genetic risk factors with human age-related macular degeneration (AMD). However, monkeys have not been reported to develop advanced atrophic or neovascular AMD. We hypothesized that dietary factors may play a role in this lack of progression to advanced disease. In particular, we examined the role of key nutrients thought to lower the risk of AMD progression and currently being tested in the AREDS2 trial: lutein and zeaxanthin--the xanthophylls that form macular pigment--and omega-3 fatty acids.
From birth until 17-22 years of age, 18 rhesus monkeys were fed semisynthetic diets devoid of lutein and zeaxanthin (L/Z), resulting in an absence of macular pigment. For 8 of these monkeys the diet was also deficient in omega-3 fatty acids, while the remaining 10 received adequate levels. The animals were monitored serially by color fundus photography and fluorescein angiography over a 12-year period and by sdOCT over 3 years.
Among monkeys fed diets lacking L/Z, 50% developed drusen by 15 years of age (equivalent to 45 human years), compared to 20% in monkeys fed normal diets. Three animals, all in the omega-3 deficient group, developed atrophic changes in the macula by 12-18 years of age. In all cases the degenerative changes first appeared in an arc approximately 1 mm superior to the fovea, the same locus where we previously found high accumulation of lipofuscin in monkeys on the same omega-3 deficient diet. The affected areas were characterized by patchy RPE disruption and pigmentary changes coincident with hyperfluorescent window defects, and increased at a linear rate over 4-7 years. sdOCT showed disruption of the RPE and IS/OS junction and large deposits extending into the photoreceptor layer.
These are the first documented cases of atrophic macular disease in nonhuman primates, and they emerged at an early age relative to typical human cases of atrophic AMD. These findings provide support for the role of L/Z and omega-3 fatty acids as important factors in progression to advanced AMD. Macaque monkeys can provide a uniquely relevant model for studying factors contributing to age-related macular disease.
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