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      Lipid Composition of the Human Eye: Are Red Blood Cells a Good Mirror of Retinal and Optic Nerve Fatty Acids?

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          Abstract

          Background

          The assessment of blood lipids is very frequent in clinical research as it is assumed to reflect the lipid composition of peripheral tissues. Even well accepted such relationships have never been clearly established. This is particularly true in ophthalmology where the use of blood lipids has become very common following recent data linking lipid intake to ocular health and disease. In the present study, we wanted to determine in humans whether a lipidomic approach based on red blood cells could reveal associations between circulating and tissue lipid profiles. To check if the analytical sensitivity may be of importance in such analyses, we have used a double approach for lipidomics.

          Methodology and Principal Findings

          Red blood cells, retinas and optic nerves were collected from 9 human donors. The lipidomic analyses on tissues consisted in gas chromatography and liquid chromatography coupled to an electrospray ionization source-mass spectrometer (LC-ESI-MS). Gas chromatography did not reveal any relevant association between circulating and ocular fatty acids except for arachidonic acid whose circulating amounts were positively associated with its levels in the retina and in the optic nerve. In contrast, several significant associations emerged from LC-ESI-MS analyses. Particularly, lipid entities in red blood cells were positively or negatively associated with representative pools of retinal docosahexaenoic acid (DHA), retinal very-long chain polyunsaturated fatty acids (VLC-PUFA) or optic nerve plasmalogens.

          Conclusions and Significance

          LC-ESI-MS is more appropriate than gas chromatography for lipidomics on red blood cells, and further extrapolation to ocular lipids. The several individual lipid species we have identified are good candidates to represent circulating biomarkers of ocular lipids. However, further investigation is needed before considering them as indexes of disease risk and before using them in clinical studies on optic nerve neuropathies or retinal diseases displaying photoreceptors degeneration.

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          Most cited references89

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          Polyunsaturated fatty acids and inflammatory processes: New twists in an old tale.

          The n-6 fatty acid arachidonic acid (AA; 20:4n-6) gives rise to eicosanoid mediators that have established roles in inflammation and AA metabolism is a long recognised target for commonly used anti-inflammatory therapies. It has generally been assumed that all AA-derived eicosanoids are pro-inflammatory. However this is an over-simplification since some actions of eicosanoids are anti-inflammatory (e.g. prostaglandin (PG) E(2) inhibits production of some inflammatory cytokines) and it has been discovered quite recently that PGE(2) inhibits production of inflammatory leukotrienes and induces production of inflammation resolving lipoxin A(4). The n-3 fatty acids from oily fish and "fish oils", eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), are incorporated into inflammatory cell phospholipids in a time- and dose-dependent manner. They are incorporated partly at the expense of AA, but also of other n-6 fatty acids. EPA and DHA inhibit AA metabolism. Thus production of AA-derived eicosanoids is decreased by these n-3 fatty acids; this occurs in a dose-dependent manner. EPA gives rise to an alternative family of eicosanoids (e.g. PGE(3)), which frequently, but not always, have lower potency than those produced from AA. Recently a new family of EPA- and DHA-derived lipid mediators called resolvins (E- and D-series) has been described. These have potent anti-inflammatory and inflammation resolving properties in model systems. It seems likely that these mediators will explain many of the antiinflammatory actions of n-3 fatty acids that have been described. In addition to modifying the profile of lipid-derived mediators, fatty acids can also influence peptide mediator (i.e. cytokine) production. To a certain extent this action may be due to the altered profile of regulatory eicosanoids, but it seems likely that eicosanoid-independent actions are a more important mechanism. Indeed effects on transcription factors that regulate inflammatory gene expression (e.g. nuclear factor kappaB) seem to be important.
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            Blood levels of long-chain n-3 fatty acids and the risk of sudden death.

            Experimental data suggest that long-chain n-3 polyunsaturated fatty acids found in fish have antiarrhythmic properties, and a randomized trial suggested that dietary supplements of n-3 fatty acids may reduce the risk of sudden death among survivors of myocardial infarction. Whether long-chain n-3 fatty acids are also associated with the risk of sudden death in those without a history of cardiovascular disease is unknown. We conducted a prospective, nested case-control analysis among apparently healthy men who were followed for up to 17 years in the Physicians' Health Study. The fatty-acid composition of previously collected blood was analyzed by gas-liquid chromatography for 94 men in whom sudden death occurred as the first manifestation of cardiovascular disease and for 184 controls matched with them for age and smoking status. Base-line blood levels of long-chain n-3 fatty acids were inversely related to the risk of sudden death both before adjustment for potential confounders (P for trend = 0.004) and after such adjustment (P for trend = 0.007). As compared with men whose blood levels of long-chain n-3 fatty acids were in the lowest quartile, the relative risk of sudden death was significantly lower among men with levels in the third quartile (adjusted relative risk, 0.28; 95 percent confidence interval, 0.09 to 0.87) and the fourth quartile (adjusted relative risk, 0.19; 95 percent confidence interval, 0.05 to 0.71). The n-3 fatty acids found in fish are strongly associated with a reduced risk of sudden death among men without evidence of prior cardiovascular disease.
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              Docosahexaenoic acid: membrane properties of a unique fatty acid.

              Docosahexaenoic acid (DHA) with 22-carbons and 6 double bonds is the extreme example of an omega-3 polyunsaturated fatty acid (PUFA). DHA has strong medical implications since its dietary presence has been positively linked to the prevention of numerous human afflictions including cancer and heart disease. The PUFA, moreover, is essential to neurological function. It is remarkable that one simple molecule has been reported to affect so many seemingly unrelated biological processes. Although details of a molecular mode of action remain elusive, DHA must be acting at a fundamental level common to many tissues that is related to the high degree of conformational flexibility that the multiple double bonds have been identified to confer. One likely target for DHA action is at the cell membrane where the fatty acid is known to readily incorporate into membrane phospholipids. Once esterified into phospholipids DHA has been demonstrated to significantly alter many basic properties of membranes including acyl chain order and "fluidity", phase behavior, elastic compressibility, permeability, fusion, flip-flop and protein activity. It is concluded that DHA's interaction with other membrane lipids, particularly cholesterol, may play a prominent role in modulating the local structure and function of cell membranes.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                9 April 2012
                : 7
                : 4
                : e35102
                Affiliations
                [1 ]CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France
                [2 ]INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Dijon, France
                [3 ]Université de Bourgogne, UMR Centre des Sciences du Goût et de l'Alimentation, Dijon, France
                [4 ]Biology, Imaging, and Engineering of Corneal Grafts, Faculty of Medicine, Department of Ophthalmology, Saint Etienne, France
                [5 ]Department of Ophthalmology, University Hospital, Dijon, France
                University of Tennessee, United States of America
                Author notes

                Conceived and designed the experiments: NA GT PG CPCG AMB LB. Performed the experiments: OB GT SG LM SC. Analyzed the data: OB SG SC. Contributed reagents/materials/analysis tools: OB SG SC. Wrote the paper: NA OB GT PG CPCG AMB LB.

                Article
                PONE-D-11-25330
                10.1371/journal.pone.0035102
                3322172
                22496896
                f0434eff-c27e-4550-855f-31f2fa9fba66
                Acar et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 16 December 2011
                : 8 March 2012
                Page count
                Pages: 18
                Categories
                Research Article
                Biology
                Biochemistry
                Lipids
                Fatty Acids
                Fatty Alcohols
                Glycerides
                Lipid Classes
                Lipid Structure
                Blood Chemistry
                Molecular Cell Biology
                Cellular Types
                Blood Cells
                Chemistry
                Analytical Chemistry
                Chromatography
                Gas Chromatography
                Liquid Chromatography
                Medicine
                Diagnostic Medicine
                Pathology
                General Pathology
                Biomarkers
                Nutrition
                Ophthalmology
                Glaucoma
                Macular Disorders
                Retinal Disorders

                Uncategorized
                Uncategorized

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