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Retinopathy and Omega-3 Fatty Acids

Retinopathy affects an estimated 4 million diabetic patients and about 40,000 premature infants in the US. Retinopathy has two critical phases: loss of vessels in the retina which leads to hypoxia, followed by new vessel growth spurred by the lack of oxygen. The new vessels grow abnormally, are malformed, leaky and over-abundant. In the later stages of the disease, the abnormal vessels pull the retina away from its supporting layer, and the detachment ultimately results in blindness.

The role of omega-3 lipids in angiogenesis is beginning to be defined, and it appears that EPA and DHA are involved in regulating vessel loss and neo-vascularization.

In a study published in the July issue of Nature Medicine, omega-3 fatty acids protected against the development and progression of retinopathy in mice. It was found that increasing tissue levels of EPA and DHA decreases the area of vascular loss in the retina by increasing normal vessel regrowth after injury, and by reducing the hypoxic stimulus for growth of abnormal vessels.

The study was a collaborative effort by researchers at Children's Hospital Boston, Brigham and Women's Hospital, Massachusetts General Hospital, the University of Göteborg in Sweden, and the National Eye Institute. The authors concluded that "supplementing omega-3 polyunsaturated fatty acid intake may be of benefit in preventing retinopathy".

Study Summary

Mice subjected to oxygen-induced retinopathy were fed isocaloric diets enriched with 2% fatty acids - either omega-3 (EPA and DHA) or omega-6 (arachidonic acid). Additionally, the researchers also examined retinopathy in the Fat-1 model. Fat-1 mice are genetically altered to convert omega-6 to omega-3 - a conversion that humans and other mammals cannot do.

Mice receiving the omega-3 rich diet were observed to have 40-50% less initial retinal vessel loss compared to omega-6 fed mice. As a result, the omega-3 group had a similar 40-50% reduction in pathological vessel growth. The results were virtually identical in the Fat-1 mice, confirming that increased retinal omega-3 levels inhibited neo-vascularization.

Omega-3 Protective Mechanism

The investigators demonstrated that the omega-3 diet suppressed production of the cytokine called TNF-alpha, reducing the inflammatory response in the retina. In contrast, the arachidonic enriched diet increased TNF-alpha production. The retinas of the omega-3 group also had higher levels of neuroprotectin D1 and resolvin D1 (both derived from DHA), and resolvin E1, which is derived from EPA. These compounds also potently protected against pathological vessel growth, and were not detected in retinas of the omega-6 fed mice.

Commentary

"It is remarkable that with only a 2% change in dietary omega-3 intake, we observed an approximate 40-50% decrease in retinopathy severity", commented one of the study's lead authors Dr. Kim Connor. "Our studies suggest that after initial loss, vessels re-grew more quickly and efficiently in the omega-3 fed mice", said Connor. "This increased the oxygen supply to retinal tissue, resulting in a dampening of the inflammatory alarm signals that lead to pathological vessel growth".

According to the other lead author, Dr. John Paul SanGiovanni, "this is a major conceptual advance in the effort to identify modifiable factors that may influence inflammatory processes implicated in the development of common sight-threatening retinal disease".

The American Diabetic Association currently advises people with diabetes to consume more omega-3 to lower their risk of heart disease. If the findings of this study are confirmed in humans, fish oil may also lessen the risk for one of the long-term complications of diabetes, retinopathy. A clinical trial at Children's Hospital Boston is set to test the effects of omega-3 supplementation in premature infants at risk of retinopathy.

Reference

1. Connor KM et al. Increased dietary intake of 3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nature Medicine 13:868-874, 2007.