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Omega-3s Slow AMD in Animal Model

It is known that omega-3 fatty acids, particularly DHA, play an important role in the layer of nerve cells in the retina, and studies have already reported that omega-3 may protect against the onset of AMD. A meta-analysis, for example, reported in the June, 2008 issue of the Archives of Ophthalmology found that a high intake of omega-3s and fish may reduce the risk of AMD by up to 38%. The Australian authors of this review noted that the benefits of omega-3 were most pronounced against more advanced AMD, while twice weekly fish consumption was associated with a lower risk of both early and late AMD (1).

In line with the epidemiologic data, are the results of a new National Eye Institute study which found that omega-3 fatty acids could retard the progression of lesions in a murine mouse model of AMD (2). Even more intriguing are the findings that mice in the high omega-3 group displayed some reversion of the lesions.

Study Design and Methods

The study evaluated the effects of a high omega-3 diet on the retinas of Cc12 - / - / Cx3cr1- / - mice - a model that develops AMD-like retinal lesions that include focal deep retinal lesions, abnormal retinal pigment epithelium, photoreceptor degeneration, and accumulation of A2E, a component of human retinal lipofuscin (an aging pigment and likely product of lipid peroxidation).

The mice were raised on low or high omega-3 diets, and clinical endpoints were measured using fundus photography, histopathology, transmission electron microscopy, A2E extraction and enzyme-linked immunoabsorbant assay to evaluate serum prostaglandin levels.

Results

Mice that were fed the high omega-3 diet showed a slower progression of lesions compared to the low omega-3 fed mice. Some mice ingesting the high omega-3 diet exhibited regression of lesions. No retinal lesions were noted in the normal wild mice used as controls and fed a regular diet.

Compared to the low omega-3 group, mice consuming the omega-3 enriched diet had lower levels of inflammatory molecules such as prostaglandin E2 and leukotriene B4, and higher levels of anti-inflammatory mediators such as prostaglandin D2. Higher omega-3 also resulted in lower IL-6 transcript levels and concentrations of ocular TNF-alpha, an inflammatory cytokine.

Comments

In summary, a diet enriched in EPA and DHA ameliorated the progression of retinal lesions in this useful animal model of AMD. These results are supportive of the findings from population health studies, and await further confirmation in humans by the AREDS 2 trial in progress.

EPA and DHA are concentrated in the retina and retinal vascular endothelium, and DHA accounts for about 50% of the lipids in photoreceptor rod outer segments. Vital retinal functions, including damage repair, depend on the existence of adequate levels of DHA.

In the eye, the omega-3 fatty acids and their derivatives play an extensive role in many biologic processes such as the inflammatory cascade, apoptosis and neuroprotection. In this study, the researchers focused on the function of the omega-3s in inflammation, since the role of inflammation in the pathogenesis of AMD is evident. Arachidonic acid, an omega-6 fatty acid, is the starting material for the synthesis of pro-inflammatory mediators such as various cytokines. When fish oil is provided, EPA and DHA are incorporated into cellular membranes at the expense of arachidonic acid.

References

1. Chong EW, et al. Dietary omega-3 fatty acid and fish intake in the primary prevention of age-related macular degeneration: a systematic review and meta-analysis. Archives of Ophthalmology 126:826-33, 2008.
2. Tuo J, et al. A high omega-3 fatty acid diet reduces retinal lesions in a murine model of macular degeneration. American Journal of Pathology 175:799-807, 2009.