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Anda Cornea, Laurie Renner, Sawan Hurst, Trevor McGill, Mark Pennesi, Kay Rittenhouse, Marvin Sperling, Joachim Fruebis, Martha Neuringer; Dominantly Inherited Early Onset Maculopathy in Japanese Macaques: Drusen Progression. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4109.
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© ARVO (1962-2015); The Authors (2016-present)
Japanese macaques (Macaca fuscata) exhibit a syndrome of early onset, progressive, dominantly inherited drusenoid maculopathy. Subretinal drusen deposits in this species show the same morphological and immunohistochemical characteristics as drusen in human patients with age-related macular degeneration (AMD), and therefore they provide a particularly useful model for translational studies. We obtained repeated retinal fundus images of affected animals and developed a novel image analysis method to quantify drusen extent and estimate rates of progression.
Serial color retinal fundus photographs were obtained from 20 Japanese macaques with the dominant drusen phenotype at 3-month intervals over a 9- to 12-month period. The animals were 4-20 years old with a wide range of drusen severity; all were members of a troop resident at ONPRC since 1964. At each time, 5 images were analyzed to increase reliability. Images were segmented into the central 1 mm and a 1-6 mm annulus. A machine learning algorithm using advanced Weka segmentation (University of Waikato) was implemented to discriminate and quantify drusen, and rates of progression were determined.
In the central macula, the initial extent of drusen ranged from <1% to 46% of the total area, with older animals showing more severe drusen loads. The rate of progression ranged from <1% to >20% (mean 5.4%) of the area of the central macula per year, largely depending on the initial area occupied by drusen. As a percentage of initial drusen area, rates of progression averaged 1.8% per year. In the 1-6 mm annulus, the initial percent area occupied by drusen ranged from 0.2-9% and increased at an average rate of 1.5% of area per year, or 1.2% of initial drusen area. A companion study is examining the relationship between these estimates of drusen load and cone densities measured by adaptive optics.
This maculopathy has close phenotypic similarity to human AMD. A similar syndrome was reported in cynomolgus macaques (Umeda et al., IOVS 46:683-691, 2005). Only higher nonhuman primates possess a macula, and macaques with naturally occurring macular disease syndromes provide a valuable resource for probing macular disease pathogenesis and for preclinical testing of AMD therapies.
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