79 articles - 10.09.10
1: Mol Vis. 2010 Mar 2;16:320-9.
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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PMID: 20216940 [PubMed - indexed for MEDLINE]2: Prostaglandins Leukot Essent Fatty Acids. 2010 Apr-Jun;82(4-6):319-25. Epub 2010 Mar 3.
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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PMID: 20202804 [PubMed - indexed for MEDLINE]3: Curr Eye Res. 2009 Nov;34(11):928-38.
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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PMID: 19958109 [PubMed - indexed for MEDLINE]4: Invest Ophthalmol Vis Sci. 2010 Mar;51(3):1755-64. Epub 2009 Nov 11.
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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PMID: 19907026 [PubMed - indexed for MEDLINE]5: Curr Med Chem. 2009;16(34):4511-26.
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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PMID: 19903153 [PubMed - indexed for MEDLINE]6: Am J Clin Nutr. 2009 Dec;90(6):1601-7. Epub 2009 Oct 7.
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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PMID: 19812176 [PubMed - indexed for MEDLINE]7: Exp Eye Res. 2009 Dec;89(6):840-53. Epub 2009 Jul 21.
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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PMID: 19627986 [PubMed - indexed for MEDLINE]8: J Neurochem. 2009 Sep;110(6):1863-75. Epub 2009 Jul 17.
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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PMID: 19627444 [PubMed - indexed for MEDLINE]9: Am J Pathol. 2009 Aug;175(2):799-807. Epub 2009 Jul 16.
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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PMID: 19608872 [PubMed - indexed for MEDLINE]10: Mol Vis. 2009 Jun 13;15:1185-93.
Li F, Marchette LD, Brush RS, Elliott MH, Le YZ, Henry KA, Anderson AG, Zhao C, Sun X, Zhang K, Anderson RE.
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
PURPOSE: Dominant Stargardt macular dystrophy (STGD3) is caused by several different mutations in a gene named ELOVL4, which shares sequence homologies with a family of genes that encode proteins involved in the ELOngation of Very Long chain fatty acids. Studies have suggested that patients with STGD3 have aberrant metabolism of docosahexaenoic acid (DHA, 22:6n3), the major polyunsaturated fatty acid (PUFA) in retinal rod outer segment membranes. We tested the effect of DHA on the progression of retinal degeneration in transgenic mice that express one of the mutations identified in STGD3. METHODS: Transgenic mice expressing mutant human ELOVL4 (TG2) were bred to mice expressing the fat-1 protein, which can convert n6 to n3 PUFA. Mice were maintained on an n3-deficient diet containing 10% safflower oil (SFO, enriched in n6 PUFA; n6/n3=273) so that four experimental groups were produced that differed only in levels of n3 PUFA and expression of the hELOVL4 transgene. These groups were identified by genotyping and named Fat1+/TG2+, Fat1(-)/TG2+, Fat1+/TG2(-), and Fat1(-)/TG2(-). All were continued on the SFO diet for 4 to 16 weeks such that those not expressing Fat1 would be deficient in n3 fatty acids. At both time points, animals were analyzed for retinal function by electroretinography (ERG), photoreceptor cell viability by outer nuclear layer (ONL) thickness measurements, fatty acid profiles in several tissues, and rhodopsin levels. RESULTS: Mice expressing the fat-1 transgene had significantly higher levels of n3 PUFA, primarily DHA, in retina, liver, and plasma lipids at 4 and 16 weeks of age. Retinal DHA levels in fat-1 mice were twice those of controls. By 16 weeks of age, mice expressing the mutant hELOVL4 transgene had a significantly greater loss of photoreceptor cells, reduced ERG amplitudes, and lower rhodopsin levels than control mice. There was no effect of retinal fatty acids on the rate of degeneration of retinas expressing the ELOVL4 transgene. CONCLUSIONS: We found no evidence that high levels of DHA in retinal membranes protected photoreceptor cells expressing mutant ELOVL4 from retinal degeneration. We conclude that DHA is not beneficial for the treatment of retinal degeneration in this animal model of human STGD3 macular dystrophy.
Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19536303&dopt=ExternalLink
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PMID: 19536303 [PubMed - indexed for MEDLINE]11: Br J Ophthalmol. 2009 Sep;93(9):1241-6. Epub 2009 Jun 9.
Chiu CJ, Klein R, Milton RC, Gensler G, Taylor A.
Laboratory for Nutrition and Vision Research, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. cj.chiu@tufts.edu
BACKGROUND: Recent information suggests that the Age-Related Eye Disease Study (AREDS) supplement, enhanced intake of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and reducing dietary glycaemic index (dGI) are protective against advanced age-related macular degeneration (AMD). METHODS: Dietary information was collected at baseline, and fundus photograph grades were obtained during the 8-year trial period from 2924 eligible AREDS AMD trial participants. Using the eye as the unit of analysis and multifailure Cox proportional-hazards regression, the risk of AMD progression was related to dietary intake in the four arms of the trial. RESULTS: Independent of AREDS supplementation, higher intakes of DHA (> or =64.0 vs <26.0 mg/day) (hazard ratio (HR) = 0.73, 95% confidence interval (CI), 0.57 to 0.94), EPA (> or =42.3 vs <12.7 mg/day) (HR = 0.74, 95% CI 0.59 to 0.94), and lower dGI (dGI, <75.2 vs > or =81.5) (HR = 0.76, 95% CI 0.60 to 0.96) were associated with a lower risk for progression to advanced AMD. Participants consuming a lower dGI and higher DHA or EPA had the lowest risk (p value for synergistic interaction <0.001). Only participants in the "placebo" (p value for antagonistic interaction = 0.006) benefited from a higher DHA intake against early AMD progression (HR = 0.58, 95% CI 0.37 to 0.92; P(trend) = 0.01). CONCLUSIONS: The findings show an association of consuming a diet rich in DHA with a lower progression of early AMD. In addition to the AREDS supplement, a lower dGI with higher intakes of DHA and EPA was associated with a reduced progression to advanced AMD. Trial registration number: NCT00000145.
Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19508997&dopt=ExternalLink
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PMID: 19508997 [PubMed - indexed for MEDLINE]12: Graefes Arch Clin Exp Ophthalmol. 2009 Sep;247(9):1191-203. Epub 2009 May 13.
Schnebelen C, Pasquis B, Salinas-Navarro M, Joffre C, Creuzot-Garcher CP, Vidal-Sanz M, Bron AM, Bretillon L, Acar N.
INRA, UMR1129 FLAVIC, Eye and Nutrition Research Group, Dijon F-21000, France.
BACKGROUND: To evaluate the effect of a dietary combination of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) compared to single PUFA supplementations on the outcome of a substantial elevation of intraocular pressure (IOP) in rats. METHODS: Sprague Dawley rats were fed for 6 months with either a control diet, a diet enriched with omega-3 PUFAs (eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA), a diet enriched with omega-6 PUFAs (gamma-linolenic acid, GLA) or a diet enriched with both omega-3 and omega-6 PUFAs (EPA + DHA and GLA). After 3 months of feeding, elevation of IOP was induced by photocoagulation of the episcleral veins, limbus and trabecular meshwork using a 532-nm laser. IOP and scotopic electroretinograms (ERGs) were monitored after the induction of IOP elevation until the end of the nutritional supplementation. Retinal morphometry and GFAP immunohistochemistry were performed 3 months after laser photocoagulation. Retinal ganglion cells (RGCs) were quantified using retrograde labelling. RESULTS: A significant rise in IOP was observed in the laser-treated eyes. PUFA supplementation did not influence the time course of IOP in the laser-treated eyes. Three months after laser photocoagulation, the activation of glial cells observed in the laser-treated eyes was significantly lower in animals fed with the EPA + DHA + GLA diet when compared to those fed the control diet, while single supplementations with either EPA + DHA or GLA were not effective. The same protective effect of the EPA + DHA + GLA combination was observed on retinal structures in the laser-treated eyes. However, PUFA supplementation did not influence either ERG b-wave amplitude or the RGC loss in the laser-treated eyes. CONCLUSIONS: This study demonstrates that a 6-month supplementation with a combination of omega-3 and omega-6 PUFAs is more effective than single supplementations, since the EPA + DHA + GLA dietary combination prevented retinal cell structure and decreased glial cell activation induced by the elevation of IOP in rats.
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=19437028&dopt=ExternalLink
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PMID: 19437028 [PubMed - indexed for MEDLINE]13: Arch Ophthalmol. 2009 May;127(5):656-65.
Tan JS, Wang JJ, Flood V, Mitchell P.
Centre for Vision Research, Department of Ophthalmology, Westmead Millennium Institute, Westmead Hospital, Westmead, NSW, Australia.
OBJECTIVE: To assess the relationship between baseline dietary fatty acids and 10-year incident age-related macular degeneration (AMD). METHODS: In an elderly Australian cohort, 3654 participants were examined at baseline and 2454 were examined 5 and/or 10 years later. We assessed AMD from retinal photographs. Participants completed a semiquantitative food frequency questionnaire. RESULTS: After adjusting for age, sex, and smoking, 1 serving of fish per week was associated with reduced risk of incident early AMD (relative risk, 0.69 [95% confidence interval, 0.49-0.98]), primarily among participants with less than the median linoleic acid consumption (0.57 [0.36-0.89]). Findings were similar for intake of long-chain omega-3 polyunsaturated fatty acids. One to 2 servings of nuts per week was associated with reduced risk of incident early AMD (relative risk, 0.65 [95% confidence interval, 0.47-0.91]). Protective associations between the intake of nuts and reduced risk of pigmentary abnormalities were seen among nonsmokers, participants with less than the median ratio of serum total to high-density lipoprotein cholesterol, and those with beta carotene intake greater than the median level. CONCLUSIONS: This study provides evidence of protection against early AMD from regularly eating fish, greater consumption of omega-3 polyunsaturated fatty acids, and low intakes of foods rich in linoleic acid. Regular consumption of nuts may also reduce AMD risk. Joint effects from multiple factors are suggested.
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=19433717&dopt=ExternalLink
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PMID: 19433717 [PubMed - indexed for MEDLINE]14: Invest Ophthalmol Vis Sci. 2009 Oct;50(10):4743-52. Epub 2009 Apr 30.
Jin Y, Arita M, Zhang Q, Saban DR, Chauhan SK, Chiang N, Serhan CN, Dana R.
Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA.
PURPOSE: Resolvins and lipoxins are lipid mediators generated from essential polyunsaturated fatty acids that are the first dual anti-inflammatory and pro-resolving signals identified in the resolution phase of inflammation. Here the authors investigated the potential of aspirin-triggered lipoxin (LX) A4 analog (ATLa), resolving (Rv) D1, and RvE1, in regulating angiogenesis in a murine model. METHODS: ATLa and RvE1 receptor expression was tested in different corneal cell populations by RT-PCR. Corneal neovascularization (CNV) was induced by suture or micropellet (IL-1 beta, VEGF-A) placement. Mice were then treated with ATLa, RvD1, RvE1, or vehicle, subconjunctivally at 48-hour intervals. Infiltration of neutrophils and macrophages was quantified after immunofluorescence staining. The mRNA expression levels of inflammatory cytokines, VEGFs, and VEGFRs were analyzed by real-time PCR. CNV was evaluated intravitally and morphometrically. RESULTS: The receptors for LXA4, ALX/Fpr-rs-2 and for RvE1, ChemR23 were each expressed by epithelium, stromal keratocytes, and infiltrated CD11b(+) cells in corneas. Compared to the vehicle-treated eye, ATLa-, RvD1-, and RvE1-treated eyes had reduced numbers of infiltrating neutrophils and macrophages and reduced mRNA expression levels of TNF-alpha, IL-1 alpha, IL-1 beta, VEGF-A, VEGF-C, and VEGFR2. Animals treated with these mediators had significantly suppressed suture-induced or IL-1 beta-induced hemangiogenesis (HA) but not lymphangiogenesis. Interestingly, only the application of ATLa significantly suppressed VEGF-A-induced HA. CONCLUSIONS: ATLa, RvE1, and RvD1 all reduce inflammatory corneal HA by early regulation of resolution mechanisms in innate immune responses. In addition, ATLa directly inhibits VEGF-A-mediated angiogenesis and is the most potent inhibitor of NV among this new genus of dual anti-inflammatory and pro-resolving lipid mediators.
Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19407006&dopt=ExternalLink
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PMID: 19407006 [PubMed - indexed for MEDLINE]15: Insight. 2008 Oct-Dec;33(4):20-5; quiz 26-7.
Cakiner-Egilmez T.
Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA. Tulay_Cakiner-Egilmez@meei.harvard.edu
The health benefits of fish oil have been known for decades. Most of the health benefits of fish oil can be attributed to the presence of omega-3 essential fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Clinical studies have suggested that DHA and EPA lower triglycerides; slow the buildup of atherosclerotic plaques; lower blood pressure slightly; as well as reduce the risk of death, heart attack, and arrhythmias. Studies have also shown that omega-3 fatty acids may slow the progression of vision loss from AMD and reverse the signs of dry eye syndrome.
Publication Types: Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19227095&dopt=ExternalLink
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PMID: 19227095 [PubMed - indexed for MEDLINE]16: Eur J Ophthalmol. 2009 Jan-Feb;19(1):100-6.
Querques G, Benlian P, Chanu B, Portal C, Coscas G, Soubrane G, Souied EH.
Department of Ophthalmology, University of Paris XII, Centre Hospitalier Intercommunal de Creteil, France. giuseppe.querques@hotmail.it
PURPOSE: To create a pilot study in order to evaluate the feasibility of a prospective case-control study of oral supplementation with fish oil (docosahexaenoic acid [DHA]; eicosapentaenoic acid [EPA]) in a population with age-related macular degeneration (AMD). METHODS: A homogeneous group of 38 patients with drusenoid pigment epithelial detachment in one eye (PED) without choroidal new vessels (CNV) was selected. A complete ophthalmologic examination, and a complete profile of fatty acids in serum (S) and in red blood cell membranes (RBCM), were recorded at day 0 and month 6. In group 1, 22 patients were orally supplemented with EPA (720 mg/day) and DHA (480 mg/day) during 6 months. In group 2, 16 patients were followed as controls. Nutritional recommendations on fish consumption were given to both groups. RESULTS: In group 1, after 6 months supplementation we observed a significant blood enrichment in EPA (EPA-S: 2.20 vs 0.79, p<0.0001 and EPA-RBCM: 2.24 vs 0.85, p<0.0001) and in DHA (DHA-S: 2.47 vs 1.56, p<0.0001 and DHA-RBCM: 6.47 vs 4.67, p<0.0001). No change was observed in group 2 despite nutritional recommendations. In this short followup, no evolution to CNV was noted in either of the two groups. Neither side effects nor dropouts were observed in either of the groups. DISCUSSION: This study supports the feasibility of a long-term double-masked prospective case-control study in an AMD population in order to evaluate a potential benefit from oral supplementation with DHA.
Publication Types: Clinical Trial, Phase I
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19123156&dopt=ExternalLink
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PMID: 19123156 [PubMed - indexed for MEDLINE]17: J Lipid Res. 2009 May;50(5):807-19. Epub 2008 Nov 20.
Tanito M, Brush RS, Elliott MH, Wicker LD, Henry KR, Anderson RE.
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
The fat-1 gene cloned from C. elegans encodes an n-3 fatty acid desaturase that converts n-6 to n-3 PUFA. Mice carrying the fat-1 transgene and wild-type controls were fed an n-3-deficient/n-6-enriched diet [fat-1- safflower oil (SFO) and wt-SFO, respectively]. Fatty acid profiles of rod outer segments (ROS), cerebellum, plasma, and liver demonstrated significantly lower n-6/n-3 ratios and higher docosahexaenoic acid (DHA) levels in fat-1-SFO compared with wt-SFO. When mice were exposed to light stress: 1) the outer nuclear layer (ONL) thickness was reduced; 2) amplitudes of the electroretinogram (ERG) were lower; 3) the number of apoptotic photoreceptor cells was greater; and 4) modification of retinal proteins by 4-hydroxyhexenal (4-HHE), an end-product of n-3 PUFA oxidation was increased in both fat-1-SFO and wt mice fed a regular lab chow diet compared with wt-SFO. The results indicate a positive correlation between the level of DHA, the degree of n-3 PUFA lipid peroxidation, and the vulnerability of the retina to photooxidative stress. In mice not exposed to intense light, the reduction in DHA resulted in reduced efficacy in phototransduction gain steps, while no differences in the retinal morphology or retinal biochemistry. These results highlight the dual roles of DHA in cellular physiology and pathology.
Publication Types: 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=19023138&dopt=ExternalLink
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PMID: 19023138 [PubMed - indexed for MEDLINE]18: J Lipid Res. 2009 Apr;50 Suppl:S400-5. Epub 2008 Nov 18.
Bazan NG.
Neuroscience Center of Excellence and Department of Ophthalmology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA. nbazan@lsuhsc.edu
Docosahexaenoic acid (DHA), the main omega-3 fatty acid, is concentrated and avidly retained in membrane phospholipids of the nervous system. DHA is involved in brain and retina function, aging, and neurological and psychiatric/behavioral illnesses. Neuroprotectin D1 (NPD1), the first-identified stereoselective bioactive product of DHA, exerts neuroprotection in models of experimental stroke by down-regulating brain ischemia reperfusion (BIR)-induced leukocyte infiltration, proinflammatory signaling, and infarct size. Moreover, NPD1 inhibits cytokine-mediated cyclooxygenase-2 (COX-2) expression. Photoreceptor membranes display the highest content of DHA of any cell. Retinal pigment epithelial cells participate in the phagocytosis of the tips of photoreceptor cells (photoreceptor outer segment renewal). There is a DHA retrieval-intercellular mechanism between both types of cells that conserves this fatty acid during this process. NPD1 promotes homeostatic regulation of the integrity of these two cells, particularly during oxidative stress, and this protective signaling may be relevant in retinal degenerative diseases. Moreover, neurotrophins are NPD1-synthesis agonists, and NPD1 content is decreased in the CA1 region of the hippocampus of Alzheimer's patients. Overall, NPD1 promotes brain cell survival via the induction of antiapoptotic and neuroprotective gene-expression programs that suppress Abeta42 production and its neurotoxicity. Thus, NPD1 elicits potent cell-protective, anti-inflammatory, prosurvival repair signaling.
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=19018037&dopt=ExternalLink
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PMID: 19018037 [PubMed - indexed for MEDLINE]19: Arch Ophthalmol. 2008 Sep;126(9):1274-9.
SanGiovanni JP, Chew EY, Agron E, Clemons TE, Ferris FL 3rd, Gensler G, Lindblad AS, Milton RC, Seddon JM, Klein R, Sperduto RD; Age-Related Eye Disease Study Research Group.
National Eye Institute, Bethesda, Maryland, USA.
OBJECTIVE: To examine the association of dietary omega-3 long-chain polyunsaturated fatty acid and fish intake with incident neovascular age-related macular degeneration (AMD) and central geographic atrophy (CGA). METHODS: Multicenter clinic-based prospective cohort study from a clinical trial including Age-Related Eye Disease Study (AREDS) participants with bilateral drusen at enrollment. Main outcome measures were incident neovascular AMD and CGA, ascertained from annual stereoscopic color fundus photographs (median follow-up, 6.3 years). We estimated nutrient and food intake from a validated food frequency questionnaire (FFQ) at baseline, with intake of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), combined EPA and DHA, and fish as primary exposures. RESULTS: After controlling for known covariates, we observed a reduced likelihood of progression from bilateral drusen to CGA among people who reported the highest levels of EPA (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.23-0.87) and EPA+DHA (OR, 0.45; 95% CI, 0.23-0.90) consumption. Levels of DHA were associated with CGA in age-, sex-, and calorie-adjusted models (OR, 0.51; 95% CI, 0.26-1.00); however, this statistical relationship did not persist in multivariable models. CONCLUSIONS: Dietary lipid intake is a modifiable factor that may influence the likelihood of developing sight-threatening forms of AMD. Our findings suggest that dietary omega-3 long-chain polyunsaturated fatty acid intake is associated with a decreased risk of progression from bilateral drusen to CGA.
Publication Types: Clinical Trial Multicenter Study Research Support, N.I.H., Extramural
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=18779490&dopt=ExternalLink
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PMID: 18779490 [PubMed - indexed for MEDLINE]20: Am J Clin Nutr. 2008 Aug;88(2):398-406.
Augood C, Chakravarthy U, Young I, Vioque J, de Jong PT, Bentham G, Rahu M, Seland J, Soubrane G, Tomazzoli L, Topouzis F, Vingerling JR, Fletcher AE.
Department of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom.
BACKGROUND: Fish intake, the major source of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may reduce the risk of age-related macular degeneration (AMD). OBJECTIVE: We investigated the association of oily fish and dietary DHA and EPA with neovascular AMD (NV-AMD). DESIGN: Participants aged >/=65 y in the cross-sectional population-based EUREYE study underwent fundus photography and were interviewed by using a food-frequency questionnaire. Fundus images were graded by the International Classification System for Age Related Maculopathy. Questionnaire data were converted to nutrient intakes with the use of food-composition tables. Survey logistic regression was used to calculate odds ratios (ORs) and 95% CIs of energy-adjusted quartiles of EPA or DHA with NV-AMD, taking into account potential confounders. RESULTS: Dietary intake data and fundus images were available for 105 cases with NV-AMD and for 2170 controls without any features of early or late AMD. Eating oily fish at least once per week compared with less than once per week was associated with a halving of the odds of NV-AMD (OR = 0.47; 95% CI: 0.33, 0.68; P = 0.002). Compared with the lowest quartile, there was a significant trend for decreased odds with increasing quartiles of either DHA or EPA. ORs in the highest quartiles were 0.32 (95% CI: 0.12, 0.87; P = 0.03) for DHA and 0.29 (95% CI: 0.11, 0.73; P = 0.02) for EPA. CONCLUSIONS: Eating oily fish at least once per week compared with less than once per week was associated with a halving of the OR for NV-AMD.
Publication Types: Multicenter Study Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=18689376&dopt=ExternalLink
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PMID: 18689376 [PubMed - indexed for MEDLINE]