Rodent of the Week: How omega-3 fatty acids promote eye health
By Shari Roan, Los Angeles Times
February 11, 2011, 1:49 p.m.
A healthy intake of omega-3 fatty acids, found in fish and fish oil supplements, has been shown to protect against retinopathy, a leading cause of blindness, particularly among people with diabetes. Now researchers have clarified how fish oil helps.
Previously, researchers from Children's Hospital Boston showed that mice fed a diet rich in omega-3s had less abnormal blood-vessel growth in the retina and less of an inflammatory response compared with mice fed omega-6 fatty acids, a less beneficial fatty acid. In the new study, published Wednesday in the journal Science Translational Medicine, the researchers showed that omega-3s promote healthy blood-vessel growth and inhibit abnormal growth. They found that a specific small molecule in omega-3s was the key to the blood-vessel stabilization.
"Our new findings give us new information on how omega-3s work that makes them an even more promising option," the lead author of the study, Dr. Lois Smith, said in a news release.
In addition, the study revealed that substances called COX enzymes, which are found in aspirin and other pain medications called NSAIDs, don't interfere with the benefits of omega-3s. However, a drug used for asthma, called zileuton, does.
The ability of fish oil to prevent eye problems is of great interest. The federal government is sponsoring a major clinical trial examining the benefits of omega-3 supplements in people with age-related macular degeneration. Smith is exploring the value of omega-3s for premature infants who are susceptible to an eye disease called retinopathy of prematurity.
Sci Transl Med 9 February 2011:
Vol. 3, Issue 69, p. 69ra12
5-Lipoxygenase Metabolite 4-HDHA Is a Mediator of the Antiangiogenic Effect of ω-3 Polyunsaturated Fatty Acids
1. Przemyslaw Sapieha1,2,*,
2. Andreas Stahl1,3,*,
3. Jing Chen1,
4. Molly R. Seaward1,
5. Keirnan L. Willett1,
6. Nathan M. Krah1,
7. Roberta J. Dennison1,
8. Kip M. Connor1,†,
9. Christopher M. Aderman1,
10. Elvira Liclican4,
11. Arianna Carughi5,6,
12. Dalia Perelman5,6,
13. Yoshihide Kanaoka7,
14. John Paul SanGiovanni8,
15. Karsten Gronert4 and
16. Lois E. H. Smith1,‡
+ Author Affiliations
1. 1Department of Ophthalmology, Harvard Medical School, Children’s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA.
2. 2Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada H1T 2M4.
3. 3University Eye Hospital Freiburg, Killianstrasse 5, Freiburg 79106, Germany.
4. 4Vision Science Program, School of Optometry, University of California, Berkeley, CA 94720, USA.
5. 5Health Research and Studies Center, Los Altos, CA 94022, USA.
6. 6Palo Alto Medical Foundation, Palo Alto, CA 94301, USA.
7. 7Department of Medicine, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02115, USA.
8. 8Division of Epidemiology and Clinical Research, National Eye Institute, Bethesda, MD 20892, USA
1. ‡To whom correspondence should be addressed. E-mail: firstname.lastname@example.org
Lipid signaling is dysregulated in many diseases with vascular pathology, including cancer, diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration. We have previously demonstrated that diets enriched in ω-3 polyunsaturated fatty acids (PUFAs) effectively reduce pathological retinal neovascularization in a mouse model of oxygen-induced retinopathy, in part through metabolic products that suppress microglial-derived tumor necrosis factor--α. To better understand the protective effects of ω-3 PUFAs, we examined the relative importance of major lipid metabolic pathways and their products in contributing to this effect. ω-3 PUFA diets were fed to four lines of mice deficient in each key lipid-processing enzyme (cyclooxygenase 1 or 2, or lipoxygenase 5 or 12/15), retinopathy was induced by oxygen exposure; only loss of 5-lipoxygenase (5-LOX) abrogated the protection against retinopathy of dietary ω-3 PUFAs. This protective effect was due to 5-LOX oxidation of the ω-3 PUFA lipid docosahexaenoic acid to 4-hydroxy-docosahexaenoic acid (4-HDHA). 4-HDHA directly inhibited endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator--activated receptor γ (PPARγ), independent of 4-HDHA’s anti-inflammatory effects. Our study suggests that ω-3 PUFAs may be profitably used as an alternative or supplement to current anti--vascular endothelial growth factor (VEGF) treatment for proliferative retinopathy and points to the therapeutic potential of ω-3 PUFAs and metabolites in other diseases of vasoproliferation. It also suggests that cyclooxygenase inhibitors such as aspirin and ibuprofen (but not lipoxygenase inhibitors such as zileuton) might be used without losing the beneficial effect of dietary ω-3 PUFA.
* ?* These authors contributed equally to this work.
* ?† Present address: Massachusetts Eye and Ear Infirmary, Angiogenesis Laboratory, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA.
* Citation: P. Sapieha, A. Stahl, J. Chen, M. R. Seaward, K. L. Willett, N. M. Krah, R. J. Dennison, K. M. Connor, C. M. Aderman, E. Liclican, A. Carughi, D. Perelman, Y. Kanaoka, J. P. SanGiovanni, K. Gronert, L. E. H. Smith, 5-Lipoxygenase Metabolite 4-HDHA Is a Mediator of the Antiangiogenic Effect of ω-3 Polyunsaturated Fatty Acids. Sci. Transl. Med. 3, 69ra12 (2011).
* Copyright (c) 2011, American Association for the Advancement of Science
Published online January 3, 2011
PEDIATRICS Vol. 127 No. 2 February 2011, pp. 223-228 (doi:10.1542/peds.2010-2427)
Fish-Oil Fat Emulsion Supplementation May Reduce the Risk of Severe Retinopathy in VLBW Infants
Dorota Pawlik, MD, PhDa, Ryszard Lauterbach, MD, PhDa, Ewa Turyk, MDb
Departments of a Neonatology and
b Ophthalmology, Jagiellonian University Medical College, Krako'w, Poland
OBJECTIVE The retina contains rods and cones that have membranes highly enriched with docosahexaenoic acid (DHA). Infants born prematurely are at risk of DHA insufficiency, because they may not have benefited from a full third trimester of the mother's lipid stores. Moreover, within the first 2 to 3 weeks of life, the main sources of lipids for premature infants are fat emulsions, which do not contain DHA.
PATIENTS AND METHODS This observational study was designed to compare the safety and efficacy outcomes of an intravenous fat emulsion that consists of fish-oil emulsion (contains DHA) with soybean and olive oil, administered from the first day of life to 40 infants who weighed <1250 g; results were obtained from a historical cohort of 44 preterm neonates who were given an emulsion of soybean and olive oil. The primary study outcomes were the occurrence of retinopathy and need for laser therapy and cholestasis. Infants in the 2 groups were comparable with regard to demographic and clinical characteristics and were subjected to the same conventional therapy.
RESULTS There was a significantly lower risk of laser therapy for infants who received an emulsion of soybean, olive oil, and fish oil (P = .023). No significant differences were found in acuity and latency of visual evoked potentials between infants in the 2 groups. There was no infant with cholestasis among those who received fish-oil emulsion, and there were 5 subjects with cholestasis in the historical group (P = .056).
CONCLUSION Fish-oil--based fat emulsion administered from the first day of life may be effective in the prophylaxis of severe retinopathy.
Key Words: retinopathy of prematurity . docosahexaenoic acid . DHA, n-3 PUFA . very low birth weight infant . parenteral nutrition
Abbreviations: DHA = docosahexaenoic acid . ROP = retinopathy of prematurity . CRIB = Clinical Risk Index for Babies . BPD = bronchopulmonary dysplasia . VEP = visual evoked potential
Accepted Oct 13, 2010.
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