A High Fat Western Diet Accelerates Progression of Drusen in Japanese Macaques with Dominantly Inherited Maculopathy

Abstract

Purpose: Japanese macaques (M. fuscata) exhibit a syndrome of early onset, progressive, dominantly inherited drusenoid maculopathy with close phenotypic similarity to human AMD. We examined effects on drusen progression of a Western diet high in saturated fat and sugar and low in carotenoids and omega-3 fatty acids.

Methods: Nine macaques with the drusen phenotype were fed the Western diet and 9 received a standard low-fat stock diet plus fruits and vegetables. Animals in both groups were 4-20 years old with a range of drusen severity. Color fundus photographs were obtained every 3 months over 18 months. Images were segmented into the central 1 mm (fovea) and a 1-6 mm annulus (perifovea), and a machine learning algorithm was used to quantify drusen.

Results: The rate of progression of drusen area was significantly higher (p<0.01) in the Western diet group (mean 5.3% of total area/yr+SEM 0.6) than in the standard diet group (1.8%/yr+0.2). In the perifovea, mean rates were 1.8%/yr (SEM 0.6) and 0.5%/yr (SEM 0.2), respectively (p=0.11). Progression rates were correlated with the initial drusen area. In the Western diet group, but not in the standard diet group, the rate of progression increased with age, particularly in the fovea. In the Western diet group after 15-18 months, but not at baseline, there was a strong correlation between the extent of foveal drusen and lymphocyte counts, suggesting a link to the systemic inflammation that high fat diets are known to induce. To investigate relationships between diet and photoreceptor structure we imaged the central macula with adaptive optics (AO) using the RTx1 camera and calculated regional cone densities. Animals on the Western diet demonstrated a downward trend in cone density with time compared to animals on the standard diet.

Conclusions: High levels of dietary total fat, saturated fat and sugar, and low levels of omega-3 fatty acids and carotenoids, particularly lutein and zeaxanthin, all have been implicated as possible nutritional risk factors for AMD. This study demonstrates that this common combined dietary pattern accelerates drusen progression in a nonhuman primate model under controlled conditions. Monkeys with naturally-occurring macular disease provide a valuable resource for evaluating macular disease pathogenesis and risk factors and for preclinical testing of AMD therapies.

Keywords: 585 macula/fovea • 618 nutritional factors • 583 lipids