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Laurie Renner, Tiffany Adevai, Alexandra Bemis, Martha Neuringer, Trevor J McGill; Fundus Autofluorescence in Monkeys Deficient in Lutein/Zeaxanthin and Omega-3 Fatty Acids. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2999.
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Macaque monkeys possess a macula and commonly develop age-related maculopathy that shares common genetic and nutritional risk factors with human age-related macular degeneration (AMD). In a life-long controlled study, we have examined the role of key nutrients thought to lower the risk of AMD progression, as tested in the AREDS2 trial: lutein and zeaxanthin--the xanthophylls that form macular pigment--and omega-3 fatty acids. Here we measured diet-related effects on fundus autofluorescence.
From birth until 18-23 years of age, 17 rhesus monkeys were fed semisynthetic diets devoid of lutein and zeaxanthin (L/Z), resulting in the absence of macular pigment. For 7 of these monkeys the diet was also deficient in omega-3 fatty acids, while 10 received adequate levels. The animals were monitored serially by fundus photography and fluorescein angiography over a 13-year period and by Spectralis sdOCT over 4 years. They were compared to age-matched monkeys fed a standard diet providing adequate L/Z and omega-3 fatty acids. Quantitative fundus autofluorescence images were collected by averaging 100 non-normalized frames with a manual intensity setting of 90. The mean grey value was measured using ImageJ for a 1 mm foveal circle, and a 1-6 mm perifoveal annulus separated into superior, inferior, nasal and temporal quadrants.
Monkeys fed L/Z-deficient diets had significantly more intense autofluorescence in both the fovea and perifovea compared to monkeys fed a standard diet, with highest levels in the omega-3 deficient group. No differences were found among the 4 quadrants.
These findings are consistent with a previous histological study that showed greater extent of lipofuscin in monkeys fed diets without L/Z, and still greater lipofuscin in those also deficient in omega-3 fatty acids. We previously reported increased incidence and accelerated progression of drusen in these L/Z deficient monkeys compared to those fed normal diets. Three animals, all in the omega-3 deficient group, developed dystrophic changes in the macula by 12-18 years of age. Together these data add support for the role of L/Z and omega-3 fatty acids as important factors in lipofuscin accumulation and macular disease progression in the retina. Macaque monkeys can provide a uniquely relevant model for studying factors contributing to age-related macular disease.
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