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Originally published online as doi:10.2353/ajpath.2009.090089 on July 16, 2009

Published online before print July 16, 2009
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(American Journal of Pathology. 2009;175:799-807.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.090089

A High Omega-3 Fatty Acid Diet Reduces Retinal Lesions in a Murine Model of Macular Degeneration

Jingsheng Tuo*, Robert J. Ross*, Alexandra A. Herzlich*, Defen Shen*, Xiaoyan Ding*, Min Zhou*, Steven L. Coon{dagger}, Nahed Hussein{ddagger}, Norman Salem, Jr{ddagger} and Chi-Chao Chan*

From the Section of Immunopathology,* Laboratory of Immunology, National Eye Institute; the Section on Neuroendocrinology,{dagger} National Institute of Child Health and Human Development; Laboratory of Membrane Biochemistry and Biophysics,{ddagger} and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland

Age-related macular degeneration (AMD) is one of the leading cause of blindness among the elderly; however, current therapy options are limited. Epidemiological studies have shown that a diet that is high in {omega}-3 polyunsaturated (n-3) fatty acids can slow disease progression in patients with advanced AMD. In this study, we evaluated the effect of such a diet on the retinas of Ccl2–/–/Cx3cr1–/– mice, a model that develops AMD-like retinal lesions that include focal deep retinal lesions, abnormal retinal pigment epithelium, photoreceptor degeneration, and A2E accumulation. Ccl2–/–/Cx3cr1–/– mice that ingested a high n-3 fatty acid diet showed a slower progression of retinal lesions compared with the low n-3 fatty acids group. Some mice that were given high levels of n-3 fatty acids had lesion reversion. We found a shunted arachidonic acid metabolism that resulted in decreased pro-inflammatory derivatives (prostaglandin E2 and leukotriene B4) and an increased anti-inflammatory derivative (prostaglandin D2). We also measured lower ocular TNF-{alpha} and IL-6 transcript levels in the mice fed a diet of high n-3 fatty acids. Our findings in these mice are in line with human studies of AMD risk reduction by long-chain n-3 fatty acids. This murine model provides a useful tool to evaluate therapies that might delay the development of AMD.


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