In the study, published in Science Translational Medicine, researchers led by scientists from Harvard Medical School, reported that metabolites from the breakdown of dietary omega-3 may directly affect the irregular blood vessel growth that leads to retinopathy.
Specifically, the omega-3 metabolite 4-hydroxy-docosahexaenoic acid (4-HDHA) was found to inhibit the sprouting and growth of irregular blood vessels.
“These results elucidate an important pathway through which omega-3 oils protect against retinopathy and perhaps exert some of their other beneficial effects: oxidation of omega-3 PUFAs by 5-LOX [5-lipoxygenase] and subsequent inhibition of angiogenesis,” said the authors, led by Dr Lois Smith, Professor of Ophthalmology at Harvard.“In addition, we report significant 4-HDHA concentrations in healthy human subjects, suggesting that our findings may apply to omega-3 PUFA action in humans.”
The authors said that although the beneficial effects of omega-3 PUFAs have been long reported, knowledge of the mechanisms by which they exert protective effects remains limited.
“Although progress has been made in understanding the protective properties of omega-3 PUFAs, we still do not know exactly which lipid-processing pathways and which molecules govern these effects in retinopathy,” the authors said.
They explained that by deciphering the pathways and bioactive metabolites through which omega-3s block abnormal vessel growth in the eye, new targeted treatments could be developed, that may add to the currently used approaches to treating retinopathy.
By genetically removing each of the four main enzymes that convert omega-3s to active metabolites one by one, the authors found that protection against retinopathy required the 5-LOX enzyme.
They found that the protective effect was due to 5-LOX oxidation of the omega-3 PUFA lipid docosahexaenoic acid (DHA) to 4-HDHA.
4-HDHA was observed to directly inhibit blood vessel growth and sprouting via the action of peroxisome proliferator–activated receptor gamma
In addition, the researchers found that large amounts of 4-HDHA were generated under stress conditions, such as those that produce retinopathy in premature newborns and diabetes.
They said that the findings could serve as the foundation for exploring new treatment regimes for retinopathy, as well as for possible treatment of systemic diseases with altered vascular growth – such as cancer.
“Our new findings give us new information on how omega-3s work that makes them an even more promising option … The cost of omega-3 supplementation is about $10 a month, versus up to $4,000 a month for anti-VEGF therapy,” said Smith, referring to the cost of current treatment techniques for retinopathy.
Smith is also currently collaborating with a Swedish research group to conduct a clinical trial of omega-3 fatty acids in premature infants, who are often deficient in omega-3. The study will measure levels of omega-3 metabolites, and follow the infants to see if they develop retinopathy.
She said that if the results are promising she will seek FDA approval to conduct a clinical trial of omega-3 in premature infants.
Source: Science Translational Medicine
Volume 3, Issue 69, doi: 10.1126/scitranslmed.3001571
“5-Lipoxygenase Metabolite 4-HDHA Is a Mediator of the Antiangiogenic Effect of w-3 Polyunsaturated Fatty Acids”
Authors: P. Sapieha, A. Stahl, J. Chen, M.R. Seaward, K.L. Willett, N.M. Krah, et al