Increased RPE and retinal thickness in monkeys deficient in lutein/zeaxanthin and omega-3 fatty acids

Abstract

 

Purpose

 

Macaque monkeys provide a uniquely relevant model for studying factors contributing to age-related macular disease. We have examined the effect on retinal health and aging of the key nutrients lutein and zeaxanthin (L/Z) and omega-3 fatty acids in a life-long controlled feeding study in rhesus monkeys. Our previous studies demonstrated that monkeys deficient in L/Z showed an absence of macular pigment, increased prevalence and early onset of drusen, and increased lipofuscin accumulation as measured by quantitative fundus autofluorescence (qFAF). Those also deficient in omega-3 fatty acids had the highest qFAF values, and some developed geographic atrophy (GA). We have now used OCT segmentation to examine effects on RPE and retinal thickness in the same animals.

 

Methods

 

From birth until 18-23 years of age, 18 rhesus monkeys were fed semisynthetic diets devoid of L/Z. For 8 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 14-year period, and by Spectralis sdOCT over 5 years. They were compared with age-matched monkeys fed a standard diet providing adequate L/Z and omega-3 fatty acids. The thickness of 9 retinal layers was measured in the fovea (central 1 mm), and the superior, inferior, nasal, and temporal quadrants of the 1-3 mm parafovea and the 3-6 mm perifovea using Spectralis automated segmentation software. Retinal morphology and RPE thickness were examined by postmortem histology.

 

Results

 

RPE thickening was observed in monkeys fed L/Z-deficient diets compared to monkeys fed a standard diet, with the most profound increases in the animals also deficient in omega-3 fatty acids. RPE thickness was correlated with qFAF values. Histological analysis of RPE thickness confirmed these observations, and loss of RPE was confirmed in areas of GA. The thickness of the outer and inner plexiform layers also was increased in monkeys deficient in L/Z and was correlated with RPE thickness.

 

Conclusions

 

Increased RPE thickness in monkeys deficient in L/Z and omega-3 fatty acids parallels similar changes in humans with early age-related macular degeneration. Results from this life-long study support the role of L/Z and omega-3 fatty acids as important factors in macular disease progression.