(fatty acids, omega 3 [mesh] | omega-3 [all] | eicosapentaen* [all] | docosahexaen* [all]) & (eye diseases [mesh] | eye disease* [all] | eye disorder* [all] | visual disease* [all] | visual disorder* [all]) (only with abstract)

209 articles - 10.09.10

1: Klin Monbl Augenheilkd. 2010 Aug 25; [Epub ahead of print]

Micronutrients and their Relevance for the Eye - Function of Lutein, Zeaxanthin and Omega-3 Fatty Acids.

Schweigert FJ, Reimann J.

Institut fur Ernahrungswissenschaft, Universitat Potsdam.

Micronutrients play an important role in function and health maintenance for the eye. Especially lutein, zeaxanthin and omega-3 fatty acids perform remarkable functions: lutein together with zeaxanthin forms the macular pigment, these carotenoids filter out the damaging blue light component from the sunlight as well as the ultraviolet light which leads to improved contrast sensitivity and less problems with screen glare. Furthermore, the macular pigment has antioxidant and anti-inflammatory effects. The omega-3 fatty acids also possess anti-inflammatory effects and, when converted into neuroprotectin, they protect against oxidative induced apoptosis in the retina. They are also responsible for the fluidity and supply to the photoreceptor membrane. These properties are important for the prevention and treatment of degenerative eye diseases like age-related macular degeneration. However, older people are often not sufficiently supplied of micronutrients in their diet. Because the supply of nutrients can hardly be achieved by dietary change, the additional intake in the form of food supplements is useful in this age group. Scientific studies have shown the positive effects of supplementation with micronutrients such as lutein/zeaxanthin, vitamin C, vitamin E, zinc and omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid (DHA and EPA). Currently available nutritional products are based in part on the ingredients of the ARED study (Age Related Eye Disease Study). According to more recent studies formulations containing lutein and omega-3 fatty acids in physiologically meaningful doses without additional beta-carotene should be preferred. 10 to 20 mg of lutein and zeaxanthin represent a safe daily dose Regarding to the context above, beta-carotene in high doses plays a minor role to the eye and is especially critical for the health of smokers. This paper summarises the functions of the presented micronutrients in the eye and can assist ophthalmologists in advising their patients. (c) Georg Thieme Verlag KG Stuttgart . New York.

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20740395&dopt=ExternalLink

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2: Am J Ophthalmol. 2010 Sep;150(3):371-375.e1. Epub 2010 Jul 8.

Association of dyslipidemia in moderate to severe meibomian gland dysfunction.

Dao AH, Spindle JD, Harp BA, Jacob A, Chuang AZ, Yee RW.

University of Texas Medical School at Houston, Department of Ophthalmology and Visual Sciences, Houston, TX 77030, USA.

PURPOSE: To determine whether meibomian gland disease, a major contributor to dry eye syndrome, is associated with dyslipidemia. DESIGN: Retrospective case-control study. METHODS: setting: Clinical practice. patient or study population: Sixty-six patients from January 2008 to July 2009 with moderate to severe meibomian gland disease whose serum lipid levels were obtained. We excluded patients who were already taking lipid-altering substances and patients with rheumatologic disease. We analyzed several parameters in prevalence of dyslipidemia (total cholesterol > 200 mg/dL, low-density lipoprotein [LDL] > 130 mg/dL, high-density lipoprotein [HDL] < 40 mg/dL, and triglycerides >150 mg/dL) in MGD patients and compared these patients to the general population as reported by data from the National Health and Nutrition Examination Survey (NHANES). main outcome measure: The prevalence of dyslipidemia (elevated total cholesterol, elevated LDL, decreased HDL, or elevated triglycerides) in patients with moderate to severe MGD. RESULTS: Patients with moderate to severe MGD had a higher incidence of dyslipidemia with respect to elevated total cholesterol (>200 mg/dL), 67.4% to 45.1% (P = .0012) when compared to population controls. There was a smaller number of MGD patients with low HDL (HDL < 40 mg/dL), 6.5%, when compared to controls, 15.7% (P = .045). The incidence of increased LDL was not statistically significant (P = .184). There was a statistically smaller number of MGD patients with high triglycerides (TG > 150 mg/dL), 15.2%, when compared to controls, 33.1% (P = .0049). CONCLUSIONS: Patients with moderate to severe MGD have a higher incidence of dyslipidemia with respect to elevated total cholesterol than the general population. Surprisingly, the component of total cholesterol that contributed most to this increase in total cholesterol came from elevated serum HDL levels. To our knowledge, elevated HDL has not been associated with any pathologic state. Patients with MGD had a statistically significant lower incidence of hypoalphalipoproteinemia (low HDL) than the general population. Patients with MGD also had a lower incidence of hypertriglyceridemia than the general population. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20619393&dopt=ExternalLink

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3: J Nutr. 2010 Aug;140(8):1462-8. Epub 2010 Jun 16.

Oral sea buckthorn oil attenuates tear film osmolarity and symptoms in individuals with dry eye.

Larmo PS, Jarvinen RL, Setala NL, Yang B, Viitanen MH, Engblom JR, Tahvonen RL, Kallio HP.

Department of Biochemistry and Food Chemistry, University of Turku, Turku, Finland.

Dry eye is a common condition that can severely impair the quality of life. We aimed to find out whether oral sea buckthorn (SB) oil, containing (n-3) and (n-6) fatty acids and antioxidants, affects dry eye. In this double-blind, randomized, parallel trial, 20- to 75-y-old women and men experiencing dry eye symptoms consumed 2 g of SB or placebo oil daily for 3 mo from fall to winter. One hundred participants were recruited and 86 completed the study. Clinical dry eye tests and symptom follow-ups were performed. Tear film hyperosmolarity is a focal factor in dry eye. There was a general increase in the osmolarity from baseline to the end of the intervention. Compared with the placebo group, the increase was significantly less in the SB group when all participants were included [intention to treat (ITT), P = 0.04] and when only participants consuming the study products for at least 80% of the intervention days were included [per protocol (PP), P = 0.02]. The maximum intensities of redness and burning tended to be lower in the SB group. In the ITT participants, the group difference was significant for redness (P = 0.04) but not for burning (P = 0.05). In the PP participants, the group difference was significant for burning (P = 0.04) but not for redness (P = 0.11). In conclusion, SB oil attenuated the increase in tear film osmolarity during the cold season and positively affected the dry eye symptoms.

Publication Types: Randomized Controlled Trial Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20554904&dopt=ExternalLink

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4: J Nutr Elder. 2010 Jan;29(1):42-71.

Nutritional supplements for older adults: review and recommendations--Part II.

Buhr G, Bales CW.

Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. buhr0001@mc.duke.edu

The use of nutritional supplements (NS) with the intention of improving health and delaying age-related chronic disease is a common practice among older adults; however, randomized controlled trials have yielded mixed results regarding the likelihood that these NS provide true health benefits. We reviewed the findings of these studies regarding the effects of NS of folic acid, vitamin B(12), vitamin B(6), and omega-3 fatty acids on health outcomes in older adults. Our conclusions include the following: Supplements of the B vitamins folate, B(12) and B(6) have been studied with regards to primary and secondary prevention of a number of major age-related chronic diseases, including cardiovascular disease (CVD), stroke, cognitive decline, and cancer. While there are some encouraging findings with regards to stroke, depression, and macular degeneration (although in only one study in the latter case), there is little evidence of benefit of B vitamin NS for delaying CVD or age-related cognitive changes. In the few cancer-related studies, the evidence of benefit is coupled with concerns about enhancing the growth of existing undiagnosed cancers. In contrast, clear health benefits have been shown with modest increases in consumption of fatty fish or fish oil supplements, including a reduction in the risk of sudden cardiac death. In addition, there is evidence that high dose fish oil supplements may lower serum triglyceride levels.

Publication Types: Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20391042&dopt=ExternalLink

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5: Mol Vis. 2010 Mar 2;16:320-9.

Neuroprotectin D1 attenuates laser-induced choroidal neovascularization in mouse.

Sheets KG, Zhou Y, Ertel MK, Knott EJ, Regan CE Jr, Elison JR, Gordon WC, Gjorstrup P, Bazan NG.

Department of Ophthalmology and the Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, USA.

PURPOSE: To examine the effects of neuroprotectin D1 (NPD1), a stereospecific derivative of docosahexaenoic acid, on choroidal neovascularization (CNV) in a laser-induced mouse model. Specifically, this was assessed by clinically grading laser-induced lesions, measuring leakage area, and volumetrically quantifying vascular endothelial cell proliferation. METHODS: C57Bl/6 mice were treated with vehicle control or NPD1, and choroidal neovascularization was induced by laser rupture of Bruch's membrane; treatment was administered throughout the first week of recovery. One and two weeks after CNV induction, fundus fluorescein angiography was performed. Angiograms were clinically graded to assess leakage severity, while leakage area was measured by image analysis of angiograms. Proliferation of vascular endothelial cells was evaluated volumetrically by three-dimensional laser confocal immunofluorescent microscopy of cytoskeletal, nuclear, and endothelial cell markers. RESULTS: At seven days after CNV induction, NPD1-treated mice had 60% fewer clinically relevant lesions than controls, dropping to 80% fewer by 14 days. NPD1 mice exhibited 25% smaller leakage area than controls at 7 days and 44% smaller area at 14 days. Volumetric immunofluorescence revealed 46% less vascular endothelial cell volume in 7-day NPD1-treated mice than in 7-day controls, and by 14 days NPD1 treatment was 68% lower than controls. Furthermore, comparison of 7- and 14-day volumes of NPD1-treated mice revealed a 50% reduction at 14 days. CONCLUSIONS: NPD1 significantly inhibits choroidal neovascularization. There are at least two possible mechanisms that could explain the neuroprotective action of NPD1. Ultimately, nuclear factor-kappaB could be inhibited with a reduction in cyclooxygenase-2 (COX-2) to reduce vascular endothelial growth factor (VEGF) expression, and/or activation of the resolution phase of the inflammatory response/survival pathways could be upregulated. Moreover, NPD1 continues to be effective after treatment is concluded, suggesting sustained protection and highlighting the potential applicability of this lipid mediator in preventing or ameliorating endothelial cell growth in pathoangiogenesis.

Publication Types: Research Support, N.I.H., Extramural

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20216940&dopt=ExternalLink

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6: Curr Opin Ophthalmol. 2010 May;21(3):184-9.

Nutritional supplements for age-related macular degeneration.

Krishnadev N, Meleth AD, Chew EY.

National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.

PURPOSE OF REVIEW: Age-related macular degeneration (AMD), a leading cause of visual loss in older adults, has limited therapeutic options. This review describes the current literature on the role of nutritional supplementation in primary and secondary prevention of AMD. RECENT FINDINGS: Many observational studies have explored the association between diet, nutrient intake, and AMD. In particular, high dietary intakes of omega-3 fatty acids, and macular xanthophylls lutein and zeaxanthin have been associated with a lower risk of prevalent and incident AMD. However, the Age-Related Eye Disease study (AREDS) is the only large-scale randomized controlled clinical trial to show a 25% beneficial effect of nutritional supplementation in reducing the risk progression to advanced AMD in patients with intermediate AMD or with advanced AMD in one eye at 5 years of follow-up. On the basis of the results of AREDS, these patients are recommended to take AREDS formulation of vitamins C, E, beta-carotene, and zinc with copper. SUMMARY: At the present time, there is insufficient evidence in the literature to recommend routine nutritional supplementation in healthy adults for primary prevention of AMD. However, patients with intermediate risk of AMD or advanced AMD in one eye should consider taking AREDS-type supplements. Observational studies have also suggested benefit from increased dietary intake of macular xanthophylls and omega-3 fatty acids. These are currently being evaluated prospectively in a randomized controlled clinical trial, the AREDS2.

Publication Types: Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20216418&dopt=ExternalLink

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7: Prostaglandins Leukot Essent Fatty Acids. 2010 Apr-Jun;82(4-6):319-25. Epub 2010 Mar 3.

Omega-3 fatty acids in dry eye and corneal nerve regeneration after refractive surgery.

He J, Bazan HE.

Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.

Dry eye (DE) is a multifactorial condition that affects the surface of the eye and induces an inflammatory response. Corneal nerves play an important role in the maintenance of a healthy ocular surface. Here we review corneal structure, nerve architecture, DE conditions, and nerve regeneration following corneal surgery and discuss how n-3 fatty acids affect the health of the cornea. Animal studies show that resolvins, compounds derived from eicosapentaenoic acid (EPA), increase tear volume and decrease inflammation induced by DE. After corneal surgery in rabbits, treatment with nerve growth factor (NGF) or pigment epithelial derived factor (PEDF) in conjunction with docosahexaenoic acid (DHA) increase nerve density and corneal epithelial cell proliferation. Increased synthesis of the novel docosanoid, neuroprotectin D1 (NPD1), was found in corneas after the animals were treated with PEDF and DHA. Topical application of these lipids derived from n-3 fatty acids could be useful in treating DE and prevent clinical complications such as cornea erosion and ulcerations. Copyright 2010 Elsevier Ltd. All rights reserved.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20202804&dopt=ExternalLink

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8: Klin Monbl Augenheilkd. 2010 Feb;227(2):120-7. Epub 2010 Feb 12.

[Importance of the nuclear factor kappaB for the primary open angle glaucoma--a hypothesis]

[Article in German]

Erb C.

Abteilung fur Augenheilkunde, Schlosspark-Klinik. carl.erb@schlosspark-klinik.de

The primary open-angle glaucoma (POAG) is an optic neuropathy which is influenced by a number of different risk factors. Some of them can induce the transcriptional factor NF-kappaB, a nuclear protein which binds to specific areas of the DNA to stimulate different genes. NF-kappaB can be activated by increased intraocular pressure, increased age, vascular diseases and by oxidative stress. In the case of POAG NF-kappaB might be overstimulated with the induction of uncontrolled biochemical reactions. Treatment strategies for reducing NF-kappaB are to reduce intraocular pressure as well as therapies with statins, omega-3-fatty acids and alpha-lipoic acid. This model is a hypothesis and is intended to provide a basis for further discussions and basic research. Georg Thieme Verlag KG Stuttgart, New York.

Publication Types: English Abstract Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20155656&dopt=ExternalLink

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9: Ocul Surf. 2010 Jan;8(1):18-28.

Essential fatty acids in the treatment of dry eye.

Rosenberg ES, Asbell PA.

Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY 10029, USA.

Essential fatty acids (EFAs) play many important roles in human biology, affecting organ systems and cellular and intracellular function. Omega-3 and omega-6 EFAs are the precursors of eicosanoids, locally acting hormones involved in mediating inflammatory processes. It is largely via the production of these eicosanoids that the essential fatty acids influence human health and disease. In general, the omega-3 derived eicosanoids are anti-inflammatory while the n-6 pathway eicosanoids promote inflammation. To date, EFAs have been primarily studied with regard to systemic diseases, particularly cardiovascular disease. Currently, no dietary recommendations of EFAs for the prevention or treatment of eye disease exist. The majority of studies concerning EFAs and eye disease have focused on diseases of the retina. This article provides an overview of the current literature regarding EFAs and dry eye disease (DED). Eight studies were identified, including six randomized controlled trials. All the studies preliminarily confirmed that there is a relationship between EFA supplementation and improvement in DED. However, strong conclusions cannot be made yet because of limitations in the research reported. The role of essential fatty acids is an important topic that would benefit from a large, multicenter, randomized clinical trial powered to reach a conclusion regarding the efficacy of essential fatty acids in the treatment of dry eye disease.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20105404&dopt=ExternalLink

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10: Med Clin (Barc). 2010 Feb 20;134(5):194-201. Epub 2010 Jan 6.

[Dietary fat intake and incidence of cataracts: The SUN Prospective study in the cohort of Navarra, Spain]

[Article in Spanish]

Martinez-Lapiscina EH, Martinez-Gonzalez MA, Guillen Grima F, Olmo Jimenez N, Zarranz-Ventura J, Moreno-Montanes J.

Departamento de Medicina Preventiva y Salud Publica, Facultad de Medicina, Clinica Universidad de Navarra, Pamplona, Navarra, Espana.

BACKGROUND AND OBJECTIVE: To evaluate prospectively the association between dietary fat intake and the incidence of cataracts in participants from the SUN cohort. PATIENTS AND METHODS: Among 12308 men and women, initially free of cataracts and followed-up for up to 6 years, we identified 182 incident cases of cataracts. Fatty acids intake was assessed by a validated 136-item semiquantitative food frequency questionnaire. Socio-demographic and anthropometric characteristics, lifestyle, health-related habits and information about medical conditions were also collected. Incident cases of cataract were ascertained by self-reports using a biennale questionnaire. RESULTS: Participants belonging to the highest category of omega-6 fatty acids intake had a non-significantly reduced risk of cataracts in the model adjusted for potential confounders but not for other fatty acids (adjusted OR: 0.58; 95% CI: 0.33, 1.03). When all types of fatty acids (saturated, monounsaturated, polyunsaturated omega-6 and polyunsaturated omega-3) were included simultaneously in the same multivariable model, this inverse association became significant (adjusted OR: 0.54 95%CI: 0.29, 0.99). There were no significant associations between other dietary fats and the risk of cataracts. CONCLUSION: High intake of omega-6 fatty acids showed a modest but significant inverse association with the development of cataracts. Copyright 2009 Elsevier Espana, S.L. All rights reserved.

Publication Types: English Abstract Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20056254&dopt=ExternalLink

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11: Cont Lens Anterior Eye. 2010 Apr;33(2):49-54; quiz 100. Epub 2009 Dec 23.

Essential fatty acids for dry eye: A review.

Roncone M, Bartlett H, Eperjesi F.

Aston University, Birmingham, UK.

PURPOSE: Dry eye is a common complaint often encountered in optometric practice. However, it is a difficult condition to treat as clinical signs do not always correlate with patient symptoms. Essential fatty acids (EFA), particularly omega-3 EFA, may be effective in dealing with the underlying causes. METHODS: A literature review was carried out on the PubMed, ScienceDirect and Ovid databases. Searches included keywords such as 'dry eye', 'essential fatty acids' and 'nutrition' to find articles relating to the treatment of dry eye syndrome (DES) with omega-3 EFAs. RESULTS: Omega-3 and -6 EFAs need to be consumed together within a reasonable ratio to be effective. Currently, typical diets in developed countries lack omega-3 EFA and this results in an overexposure to omega-6. Omega-3 supplementation has an anti-inflammatory effect, inhibiting creation of omega-6 prostaglandin precursors. Omega-3 EFAs also demonstrate anti-inflammatory action in the lacrimal gland preventing apoptosis of the secretory epithelial cells. Supplementation clears meibomitis, allowing a thinner, more elastic lipid layer to protect the tear film and cornea. CONCLUSION: Dietary supplementation of omega-3 EFA has already proven to be effective in coronary heart disease and arthritis. Safety is not a concern as it works synergistically with omega-6 in the body. Evidence suggests that supplementation with omega-3 EFA may be beneficial in the treatment and prevention of DES. 2009 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Publication Types: Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20031476&dopt=ExternalLink

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12: Curr Eye Res. 2009 Nov;34(11):928-38.

Beneficial effect of docosahexanoic acid and lutein on retinal structural, metabolic, and functional abnormalities in diabetic rats.

Arnal E, Miranda M, Johnsen-Soriano S, Alvarez-Nolting R, Diaz-Llopis M, Araiz J, Cervera E, Bosch-Morell F, Romero FJ.

Ophthalmological Mediterranean Foundation, Valencia, Spain.

PURPOSE: To assess the effect of docosahexanoic acid (DHA) and lutein (both compounds with anti-inflammatory and antioxidant properties) on experimental diabetic retinopathy. METHODS: Male Wistar rats were studied: non-diabetic controls, untreated diabetic controls, and diabetic rats were treated with DHA and lutein or the combination of DHA + insulin and lutein + insulin for 12 weeks. Oxidative stress and inflammatory markers, apoptosis, and functional tests were studied to confirm biochemical and functional changes in the retina of diabetic rats. Malondialdehyde (MDA), glutathione concentrations (GSH), and glutathione peroxidase activity (GPx) were measured as oxidative stress markers. TUNEL assay and caspase-3 immunohistochemistry and electroretinogram were performed. RESULTS: Diabetes increases oxidative stress, nitrotyrosine concentrations, and apoptosis in the retina. At 12 weeks after onset of diabetes, total thickness of retinas of diabetic rats was significantly less than that in control rats. Specifically, the thickness of the outer and inner nuclear layers was reduced significantly in diabetic rats and demonstrated a loss of cells in the GCL. These retinal changes were avoided by the administration of insulin and DHA and lutein alone or in combination with insulin. Impairment of the electroretinogram (b-wave amplitude and latency time) was observed in diabetic rats. DHA and lutein prevented all these changes even under hyperglycemic conditions. CONCLUSIONS: Lutein and DHA are capable of normalizing all the diabetes-induced biochemical, histological, and functional modifications. Specifically, the cell death mechanisms involved deserve further studies to allow the proposal as potential adjuvant therapies to help prevent vision loss in diabetic patients.

Publication Types: Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19958109&dopt=ExternalLink

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13: Invest Ophthalmol Vis Sci. 2010 Mar;51(3):1755-64. Epub 2009 Nov 11.

A role for omega-3 polyunsaturated fatty acid supplements in diabetic neuropathy.

Yee P, Weymouth AE, Fletcher EL, Vingrys AJ.

Department of Anatomy and Cell Biology, The University of Melbourne, Victoria, Australia.

PURPOSE: Diabetes results in an insulin-related disorder of lipid metabolism that reduces production of long-chain polyunsaturated fatty acids (PUFAs; e.g., docosahexanoic acid, DHA). This study considers the role that this lipid change has on retinal function. METHODS: From conception, rats (n = 56) were fed diets either balanced (n = 32) in PUFAs or deficient in omega-3 (n = 24). Half were assigned to control (n = 28) or streptozotocin (STZ: n = 28) treatment at 7 weeks of age. Key metabolic indices were assayed at 19 weeks, and retinal function was determined by electroretinogram (ERG) at 20 weeks. Retinal anatomy and lipid assays of 20-week-old animals were used to identify structural changes and tissue PUFA content. RESULTS: The systemic indices of diabetic rats were not affected by diet. Lipid composition of retinal membranes reflected the dietary manipulation, and diabetes amplified some fatty acid changes consistent with reduced desaturase activity. Diabetes produced significant reduction in rod function (-33%) only in the absence of fish oil, whereas cone responses (-46%) and inner retinal oscillatory potentials (-47%) showed either no effect of diet or a partial diet effect with a significant diabetes effect. Anatomic analysis revealed no disorder in the retinal neurons, although changes in the Muller glia were noted in diabetes, regardless of diet. CONCLUSIONS: A diet balanced in long-chain PUFAs modifies retinal lipid membranes in diabetes and prevents rod dysfunction. Dietary modification was not found in the cone or glial response but a partial improvement was evident in the OPs, most likely secondary to the larger photoreceptor output.

Publication Types: Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19907026&dopt=ExternalLink

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14: Curr Med Chem. 2009;16(34):4511-26.

Dietary n-3 PUFA vascular targeting and the prevention of tumor growth and age-related macular degeneration.

Serini S, Piccioni E, Calviello G.

Institute of General Pathology, Lgo F Vito, 1, 00168 Rome, Italy.

The protective role of dietary n-3 polyunsaturated fatty acids (PUFAs) against cardiovascular diseases has been partly related to their ability to modulate the risk condition known as "endothelial dysfunction", by reverting the endothelial alterations associated to it (reduced vascular reactivity, the proinflammatory state, and the prothrombotic properties). Moreover, vasculature represents the target for inhibition of pathologic neo-angiogenesis by n-3 PUFAs. This effect is believed to contribute to the beneficial action of these fatty acids against disorders which recognize neovascularization as a crucial pathogenetic step for their development, such as cancer and age-related macular degeneration (AMD). Many epidemiological studies have been conducted to evaluate the association between the intake of these fatty acids and the risk of developing cancer or AMD, even though contrasting and not definitive results have been obtained. Conversely, plenty of preclinical and in vitro experimental studies have provided evidence for the anti-angiogenic effects of n-3 PUFAs, mainly studying neo-angiogenesis in general (using normal endothelial cells in vitro) or as a step of cancer growth. The main aim of this review is to critically review the current evidence for the inhibition of the neo-angiogenic process exerted by n-3 PUFAs in cancer and AMD, and to identify possible molecular mechanisms that might contribute to their beneficial effects.

Publication Types: Research Support, Non-U.S. Gov't Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19903153&dopt=ExternalLink

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15: Arch Ophthalmol. 2009 Nov;127(11):1483-93.

Association between dietary fat intake and age-related macular degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS): an ancillary study of the Women's Health Initiative.

Parekh N, Voland RP, Moeller SM, Blodi BA, Ritenbaugh C, Chappell RJ, Wallace RB, Mares JA; CAREDS Research Study Group.

Department of Nutrition, Food Studies, and Public Health, New York University, New York, New York, USA.

OBJECTIVE: To evaluate the relationships between the amount and type of dietary fat and intermediate age-related macular degeneration (AMD). DESIGN: Women aged 50 to 79 years with high and low lutein intake from 3 sites of the Women's Health Initiative Observational Study were recruited into the Carotenoids in Age-Related Eye Disease Study. Fat intake from 1994 through 1998 was estimated using food frequency questionnaires, and AMD was assessed photographically from 2001 through 2004. RESULTS: Intakes of omega-6 and omega-3 polyunsaturated fatty acids, which were highly correlated (r = 0.8), were associated with approximately 2-fold higher prevalence of intermediate AMD in high vs low quintiles. However, monounsaturated fatty acid intake was associated with lower prevalence. Age interactions were often observed. In women younger than 75 years (n = 1325), total fat and saturated fatty acid intakes were associated with increased prevalence of AMD (multivariate adjusted odds ratios [95% confidence interval] for intermediate AMD, 1.7 [1.0-2.7] for quintile 5 vs quintile 1 for total fat [P = .10 for trend] and 1.6 [0.7-3.6] for saturated fatty acids [P = .23 for trend]). The associations were reversed in older women. CONCLUSIONS: These results support a growing body of evidence suggesting that diets high in several types of fat may contribute to the risk of intermediate AMD and that diets high in monounsaturated fatty acids may be protective.

Publication Types: Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19901214&dopt=ExternalLink

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16: Curr Opin Clin Nutr Metab Care. 2010 Jan;13(1):28-33.

Age-related macular degeneration and antioxidant vitamins: recent findings.

Johnson EJ.

Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 02111, USA. elizabeth.johnson@tufts.edu

PURPOSE OF REVIEW: The purpose of the present review is to evaluate the most recent evidence for a role of antioxidant nutrients in the prevention or delay in progression of age-related macular degeneration (AMD), a major cause of visual impairment and blindness in the aging population. RECENT FINDINGS: Recent human studies (>2008) report a decreased AMD risk with increased intakes of lutein/zeaxanthin, B vitamins, zinc and docosahexaenoic acid but an increased risk with increased intakes of beta-carotene and vitamin E. These latter findings are inconsistent with previous reports (<2008). SUMMARY: Findings on the association of certain antioxidants and docosahexaenoic acid support a role for nutrition in a decreased risk of AMD. The inconsistent findings of an increased risk with increased intake of beta-carotene and vitamin E warrants continued investigation into these relationships.

Publication Types: Research Support, U.S. Gov't, Non-P.H.S. Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19841580&dopt=ExternalLink

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17: Am J Clin Nutr. 2009 Dec;90(6):1601-7. Epub 2009 Oct 7.

{omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study.

Sangiovanni JP, Agron E, Meleth AD, Reed GF, Sperduto RD, Clemons TE, Chew EY; Age-Related Eye Disease Study Research Group.

National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1204, USA. jpsangio@post.harvard.edu

BACKGROUND: omega-3 (n-3) Long-chain polyunsaturated fatty acids (LCPUFAs) affect processes implicated in vascular and neural retinal pathogenesis and thus may influence the risk of developing age-related macular degeneration (AMD). OBJECTIVE: We investigated whether omega-3 LCPUFA intake was associated with a reduced likelihood of developing central geographic atrophy (CGA) and neovascular (NV) AMD. DESIGN: We undertook a nested cohort study within a multicenter phase 3 clinical trial, the Age-Related Eye Disease Study (AREDS), to study progression to advanced AMD in 1837 persons at moderate-to-high risk of this condition. The AREDS was designed to assess the clinical course, prognosis, risk factors, and nutrient-based treatments of AMD and ran from November 1992 to December 2005. We obtained baseline data on omega-3 LCPUFA intake with a validated food-frequency questionnaire. Trained fundus graders ascertained AMD status from annual stereoscopic color photographs by using standardized methods at a single reading center across a 12-y period. We applied multivariable repeated-measures logistic regression with the incorporation of generalized estimating equation methods, because this permitted determination of progression to outcome at each visit. RESULTS: Participants who reported the highest omega-3 LCPUFA intake (median: 0.11% of total energy intake) were 30% less likely than their peers to develop CGA and NV AMD. The respective odds ratios were 0.65 (95% CI: 0.45, 0.92; P <or= 0.02) and 0.68 (95% CI: 0.49, 0.94; P <or= 0.02). CONCLUSIONS: The 12-y incidence of CGA and NV AMD in participants at moderate-to-high risk of these outcomes was lowest for those reporting the highest consumption of omega-3 LCPUFAs. If these results are generalizable, they may guide the development of low-cost and easily implemented preventive interventions for progression to advanced AMD. This trial was registered at clinicaltrials.gov as NCT00594672.

Publication Types: Clinical Trial, Phase III Multicenter Study Research Support, N.I.H., Extramural

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19812176&dopt=ExternalLink

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18: Exp Eye Res. 2009 Dec;89(6):840-53. Epub 2009 Jul 21.

Red blood cell plasmalogens and docosahexaenoic acid are independently reduced in primary open-angle glaucoma.

Acar N, Berdeaux O, Juaneda P, Gregoire S, Cabaret S, Joffre C, Creuzot-Garcher CP, Bretillon L, Bron AM.

Eye and Nutrition Research Group, UMR FLAVIC, INRA, Dijon, France. acar@dijon.inra.fr

Among several theories involved in the pathogenesis of primary open-angle glaucoma (POAG), the vascular theory considers the disease to be a consequence of reduced ocular blood flow associated with red blood cell abnormalities. Red blood cell membrane structure and function are influenced by their phospholipid composition. We investigated whether specific lipid entities that may affect the membrane physiology, namely, polyunsaturated fatty acids (PUFAs) and plasmalogens, are modified in POAG and whether these potential variations are related to the stage of glaucoma. Blood samples were collected from 31 POAG patients and 10 healthy individuals. The stage of glaucoma was determined according to the Hodapp and Parrish classification. Lipids were extracted from red blood cell membranes and individual phospholipid species were quantified by liquid chromatography combined with mass spectrometry using triple quadrupole technology. POAG patients had reduced erythrocyte levels of phosphatidyl-choline (PC) carrying docosahexaenoic acid (DHA). POAG patients also displayed lower levels of choline plasmalogens (PlsC) carrying PUFAs other than DHA. These differences were greater as the severity of the disease increased. Linear regressions predicted that red blood cell PlsC levels would decrease years before clinical symptoms, whereas the levels of PC carrying DHA were linearly correlated to visual field loss. Our data demonstrate the selective loss of some individual phospholipid species in red blood cell membranes, which may partly explain their loss of flexibility in POAG.

Publication Types: Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19627986&dopt=ExternalLink

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19: J Neurochem. 2009 Sep;110(6):1863-75. Epub 2009 Jul 17.

Docosahexaenoic acid attenuates microglial activation and delays early retinal degeneration.

Ebert S, Weigelt K, Walczak Y, Drobnik W, Mauerer R, Hume DA, Weber BH, Langmann T.

Institute of Human Genetics, University of Regensburg, Regensburg, Germany.

Microgliosis is a common phenomenon in neurodegenerative disorders including retinal dystrophies. We performed a detailed characterization of activated microglia in the retinoschisin (Rs1h)-deficient (Rs1h(-/Y)) mouse model of inherited retinal degeneration. To visualize and isolate microglia, we crossed Rs1h(-/Y) animals with transgenic MacGreen mice, which express green fluorescent protein under the control of the macrophage-specific csf1r promoter. Activated microglia were detected in retinal sections and whole-mounts of early postnatal MacGreen/Rs1h(-/Y) mice before the onset of overt neuronal cell death. These activated microglia contained prominent lipid droplets and analysis of the retinal lipid composition showed decreased docosahexaenoic acid (DHA) levels in Rs1h(-/Y) retinas. To establish a link between microglia activation, reduced DHA levels, and neurodegeneration, a dietary intervention study was performed. Female Rs1h(-/-) mice and their Rs1h(-/Y) litter were either subjected to a diet enriched with DHA, or a control chow lacking DHA. Supplementation with DHA enhanced photoreceptor survival and converted activated microglia to a quiescent phenotype. Furthermore, DHA, but not docosapentaenoic acid or adrenic acid reduced pro-inflammatory gene expression, migration, and lipid accumulation of cultured BV-2 microglia. We conclude that retinal DHA levels control the activity of microglia and thereby may affect the progression and extent of retinal degeneration.

Publication Types: Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19627444&dopt=ExternalLink

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20: Am J Pathol. 2009 Aug;175(2):799-807. Epub 2009 Jul 16.

A high omega-3 fatty acid diet reduces retinal lesions in a murine model of macular degeneration.

Tuo J, Ross RJ, Herzlich AA, Shen D, Ding X, Zhou M, Coon SL, Hussein N, Salem N Jr, Chan CC.

10/10N103, NIH/NEI, 10 Center Dr., Bethesda, MD 20892-1857, USA.

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 E(2) and leukotriene B(4)) and an increased anti-inflammatory derivative (prostaglandin D(2)). 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.

Publication Types: Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19608872&dopt=ExternalLink

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