Lutein: More than just a filter for blue light

Lutein is concentrated in the primate retina, where together with zeaxanthin it forms the macular pigment. Traditionally lutein is characterized by its blue light filtering and anti-oxidant properties. Eliminating lutein from the diet of experimental animals results in early degenerative signs in the retina while patients with an acquired condition of macular pigment loss (Macular Telangiectasia) show serious visual handicap indicating the importance of macular pigment. Whether lutein intake reduces the risk of age related macular degeneration (AMD) or cataract formation is currently a strong matter of debate and abundant research is carried out to unravel the biological properties of the lutein molecule. SR-B1 has recently been identified as a lutein binding protein in the retina and this same receptor plays a role in the selective uptake in the gut. In the blood lutein is transported via high-density lipoproteins (HDL). Genes controlling SR-B1 and HDL levels predispose to AMD which supports the involvement of cholesterol/lutein transport pathways. Apart from beneficial effects of lutein intake on various visual function tests, recent findings show that lutein can affect immune responses and inflammation. Lutein diminishes the expression of various ocular inflammation models including endotoxin induced uveitis, laser induced choroidal neovascularization, streptozotocin induced diabetes and experimental retinal ischemia and reperfusion. In vitro studies show that lutein suppresses NF kappa-B activation as well as the expression of iNOS and COX-2. Since AMD has features of a chronic low-grade systemic inflammatory response, attention to the exact role of lutein in this disease has shifted from a local effect in the eye towards a possible systemic anti-inflammatory function.

[1]  B. Chew,et al.  Dietary lutein inhibits mouse mammary tumor growth by regulating angiogenesis and apoptosis. , 2003, Anticancer research.

[2]  T. Wong,et al.  Modulation of humoral and cell-mediated immune responses by dietary lutein in cats. , 2000, Veterinary immunology and immunopathology.

[3]  W. V. Berghe,et al.  N-Acetyl-l-Cysteine Inhibits Primary Human T Cell Responses at the Dendritic Cell Level: Association with NF-κB Inhibition , 1999, The Journal of Immunology.

[4]  M. Calvo Lutein: A Valuable Ingredient of Fruit and Vegetables , 2005, Critical reviews in food science and nutrition.

[5]  K. Tomer,et al.  Blue light induced A2E oxidation in rat eyes — experimental animal model of dry AMD , 2010, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[6]  F. J. Romero,et al.  Lutein and docosahexaenoic acid prevent cortex lipid peroxidation in streptozotocin-induced diabetic rat cerebral cortex , 2010, Neuroscience.

[7]  N. Afshari,et al.  Nutrition and the prevention of cataracts , 2008, Current opinion in ophthalmology.

[8]  T. Berendschot,et al.  Quantification of reduced macular pigment optical density in the central retina in macular telangiectasia type 2. , 2009, Experimental eye research.

[9]  P. Borel,et al.  Genetic variants in BCMO1 and CD36 are associated with plasma lutein concentrations and macular pigment optical density in humans , 2011, Annals of medicine.

[10]  J. van de Kraats,et al.  Lutein and zeaxanthin measured separately in the living human retina with fundus reflectometry. , 2008, Investigative ophthalmology & visual science.

[11]  Y. Peng,et al.  Micronutrient concentrations in paired skin and plasma of patients with actinic keratoses: effect of prolonged retinol supplementation. , 1993, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[12]  E. Norkus,et al.  Serum Lutein Response Is Greater from Free Lutein Than from Esterified Lutein during 4 Weeks of Supplementation in Healthy Adults , 2010, Journal of the American College of Nutrition.

[13]  T. Berendschot,et al.  Lens aging in relation to nutritional determinants and possible risk factors for age-related cataract. , 2002, Archives of ophthalmology.

[14]  J. Weststrate,et al.  Amount of fat in the diet affects bioavailability of lutein esters but not of α-carotene, β-carotene, and vitamin E in humans , 2000 .

[15]  M. Failla,et al.  Xanthophylls and α-Tocopherol Decrease UVB-Induced Lipid Peroxidation and Stress Signaling in Human Lens Epithelial Cells , 2004 .

[16]  K. Tsubota,et al.  Neuroprotective effect of an antioxidant, lutein, during retinal inflammation. , 2009, Investigative ophthalmology & visual science.

[17]  P. Bernstein,et al.  Identification of StARD3 as a lutein-binding protein in the macula of the primate retina. , 2011, Biochemistry.

[18]  B. Clevidence,et al.  Association of carotenoids with human plasma lipoproteins. , 1993, Methods in enzymology.

[19]  J. Erdman,et al.  Concentrations of selected carotenoids and vitamin A in human liver, kidney and lung tissue. , 1991, The Journal of nutrition.

[20]  S. Leeson,et al.  Dietary Lutein Influences Immune Response in Laying Hens , 2006 .

[21]  Bryan K. Smith,et al.  Effects of omega-3 fatty acid supplementation and exercise on low-density lipoprotein and high-density lipoprotein subfractions. , 2004, Metabolism: clinical and experimental.

[22]  J. M. Fernández-Sevilla,et al.  Biotechnological production of lutein and its applications , 2010, Applied Microbiology and Biotechnology.

[23]  R. Bone,et al.  Carotenoids in the human retina , 1999 .

[24]  M. Neuringer,et al.  Serum lutein concentrations in healthy term infants fed human milk or infant formula with lutein , 2009, European journal of nutrition.

[25]  A. Ismail,et al.  Carotenoids and Their Isomers: Color Pigments in Fruits and Vegetables , 2011, Molecules.

[26]  Martin Oppermann,et al.  Systemic Complement Activation in Age-Related Macular Degeneration , 2008, PloS one.

[27]  Stuart Richer,et al.  Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). , 2004, Optometry.

[28]  F. J. Romero,et al.  Lutein effect on retina and hippocampus of diabetic mice. , 2006, Free radical biology & medicine.

[29]  J. Gray,et al.  Deposition of Carotenoids in Eggs from Hens Fed Diets Containing Saponified and Unsaponified Oleoresin Paprika , 1996 .

[30]  Fred Hendrikse,et al.  Correspondence between retinal reflectometry and a flicker-based technique in the measurement of macular pigment spatial profiles. , 2009, Journal of biomedical optics.

[31]  P. Bowen,et al.  Esterification does not impair lutein bioavailability in humans. , 2002, The Journal of nutrition.

[32]  A. Alves-Rodrigues,et al.  The science behind lutein. , 2004, Toxicology letters.

[33]  Myung Cheul Kim,et al.  Lutein is a competitive inhibitor of cytosolic Ca2+‐dependent phospholipase A2 , 2010, The Journal of pharmacy and pharmacology.

[34]  C. Itsiopoulos,et al.  Plasma carotenoids and diabetic retinopathy , 2008, British Journal of Nutrition.

[35]  P. Bernstein,et al.  Retinal tubulin binds macular carotenoids. , 1997, Investigative ophthalmology & visual science.

[36]  K. Tsubota,et al.  Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes , 2010, Diabetologia.

[37]  J. Weststrate,et al.  Amount of fat in the diet affects bioavailability of lutein esters but not of alpha-carotene, beta-carotene, and vitamin E in humans. , 2000, The American journal of clinical nutrition.

[38]  W. Subczynski,et al.  Location of macular xanthophylls in the most vulnerable regions of photoreceptor outer-segment membranes. , 2010, Archives of biochemistry and biophysics.

[39]  F. Delori,et al.  Bimodal spatial distribution of macular pigment: evidence of a gender relationship. , 2006, Journal of the Optical Society of America. A, Optics, image science, and vision.

[40]  L. Rapp,et al.  Lutein and zeaxanthin concentrations in rod outer segment membranes from perifoveal and peripheral human retina. , 2000, Investigative ophthalmology & visual science.

[41]  M. Bots,et al.  Serum carotenoids and vitamins in relation to markers of endothelial function and inflammation , 2004, European Journal of Epidemiology.

[42]  E. Agrón,et al.  Complement component C5a Promotes Expression of IL-22 and IL-17 from Human T cells and its Implication in Age-related Macular Degeneration , 2011, Journal of Translational Medicine.

[43]  M. Darvin,et al.  Raman spectroscopic analysis of the carotenoid concentration in egg yolks depending on the feeding and housing conditions of the laying hens , 2012, Journal of biophotonics.

[44]  A. J. Wenzel,et al.  Diet and serum carotenoid concentrations affect macular pigment optical density in adults 45 years and older. , 2005, The Journal of nutrition.

[45]  M. Pahor,et al.  Serum carotenoids and markers of inflammation in nonsmokers. , 2000, American journal of epidemiology.

[46]  M. Gross,et al.  Immunomodulating actions of carotenoids: enhancement of in vivo and in vitro antibody production to T-dependent antigens. , 1994, Nutrition and cancer.

[47]  K. Yeum,et al.  Carotenoid bioavailability and bioconversion. , 2003, Annual review of nutrition.

[48]  F. Delori,et al.  Long term dietary supplementation with zeaxanthin reduces photoreceptor death in light-damaged Japanese quail. , 2002, Experimental eye research.

[49]  J. Gerss,et al.  Nutritional manipulation of primate retinas, V: effects of lutein, zeaxanthin, and n-3 fatty acids on retinal sensitivity to blue-light-induced damage. , 2011, Investigative ophthalmology & visual science.

[50]  R. Milton,et al.  C-reactive protein and homocysteine are associated with dietary and behavioral risk factors for age-related macular degeneration. , 2006, Nutrition.

[51]  A. Bird,et al.  Macular pigment in the human retina: histological evaluation of localization and distribution , 2008, Eye.

[52]  H. Hense,et al.  Determinants of macular pigment optical density and its relation to age-related maculopathy: results from the Muenster Aging and Retina Study (MARS). , 2011, Investigative ophthalmology & visual science.

[53]  A. Morland,et al.  Macular pigments: their characteristics and putative role , 2004, Progress in Retinal and Eye Research.

[54]  K. McGraw,et al.  Carotenoids, Immunocompetence, and the Information Content of Sexual Colors: An Experimental Test , 2003, The American Naturalist.

[55]  F. Pashkow,et al.  Astaxanthin: a novel potential treatment for oxidative stress and inflammation in cardiovascular disease. , 2008, The American journal of cardiology.

[56]  B. Hammond,et al.  The influence of dietary lutein and zeaxanthin on visual performance. , 2010, Journal of food science.

[57]  V. Baskaran,et al.  Effect of micellar lipids, dietary fiber and β-carotene on lutein bioavailability in aged rats with lutein deficiency. , 2011, Nutrition.

[58]  Elizabeth J Johnson,et al.  The selective retention of lutein, meso-zeaxanthin and zeaxanthin in the retina of chicks fed a xanthophyll-free diet. , 2007, Experimental eye research.

[59]  D. Snodderly,et al.  Relation among serum and tissue concentrations of lutein and zeaxanthin and macular pigment density. , 2000, The American journal of clinical nutrition.

[60]  R. Hogg,et al.  The effect of lutein- and zeaxanthin-rich foods v. supplements on macular pigment level and serological markers of endothelial activation, inflammation and oxidation: pilot studies in healthy volunteers , 2012, British Journal of Nutrition.

[61]  R. Selvaraj,et al.  Lutein and eicosapentaenoic acid interact to modify iNOS mRNA levels through the PPARgamma/RXR pathway in chickens and HD11 cell lines. , 2006, The Journal of nutrition.

[62]  A. Munnich,et al.  rs5888 Variant of SCARB1 Gene Is a Possible Susceptibility Factor for Age-Related Macular Degeneration , 2009, PloS one.

[63]  G. Britton,et al.  Oxidation of carotenoids by free radicals: relationship between structure and reactivity. , 1997, Biochimica et biophysica acta.

[64]  K. So,et al.  Effect of lutein on retinal neurons and oxidative stress in a model of acute retinal ischemia/reperfusion. , 2009, Investigative ophthalmology & visual science.

[65]  F. Ferris,et al.  The effect of lutein and zeaxanthin supplementation on metabolites of these carotenoids in the serum of persons aged 60 or older. , 2006, Investigative ophthalmology & visual science.

[66]  F. J. Romero,et al.  Beneficial Effect of Docosahexanoic Acid and Lutein on Retinal Structural, Metabolic, and Functional Abnormalities in Diabetic Rats , 2009, Current eye research.

[67]  Elizabeth J Johnson,et al.  Intake of lutein and zeaxanthin differ with age, sex, and ethnicity. , 2010, Journal of the American Dietetic Association.

[68]  T. Wong,et al.  Dietary lutein stimulates immune response in the canine. , 2000, Veterinary immunology and immunopathology.

[69]  H. Furr,et al.  Intestinal absorption and tissue distribution of carotenoids , 1997 .

[70]  J. von Lintig,et al.  A class B scavenger receptor mediates the cellular uptake of carotenoids in Drosophila , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[71]  Lawrence A. Yannuzzi,et al.  Dietary Carotenoids, Vitamins A, C, and E, and Advanced Age-Related Macular Degeneration , 1994 .

[72]  K. Clément,et al.  Dietary factors and low-grade inflammation in relation to overweight and obesity , 2011, British Journal of Nutrition.

[73]  O. Sommerburg,et al.  Lutein and zeaxanthin are associated with photoreceptors in the human retina. , 1999, Current eye research.

[74]  K. Ha,et al.  Astaxanthin inhibits nitric oxide production and inflammatory gene expression by suppressing I ( kappa ) B kinase-dependent NF-kappaB activation , 2010 .

[75]  Suk-yee Li,et al.  Lutein Protects RGC-5 Cells Against Hypoxia and Oxidative Stress , 2010, International journal of molecular sciences.

[76]  Martha Neuringer,et al.  Nutritional manipulation of primate retinas, II: effects of age, n-3 fatty acids, lutein, and zeaxanthin on retinal pigment epithelium. , 2004, Investigative ophthalmology & visual science.

[77]  L. Yonekura,et al.  Keto-carotenoids are the major metabolites of dietary lutein and fucoxanthin in mouse tissues. , 2010, The Journal of nutrition.

[78]  J. Cruysberg,et al.  Patients with Sjögren-Larsson syndrome lack macular pigment. , 2010, Ophthalmology.

[79]  S. Beatty,et al.  The respective relationships between lipoprotein profile, macular pigment optical density, and serum concentrations of lutein and zeaxanthin. , 2010, Investigative ophthalmology & visual science.

[80]  H. Hense,et al.  The ringlike structure of macular pigment in age-related maculopathy: results from the Muenster Aging and Retina Study (MARS). , 2011, Investigative Ophthalmology and Visual Science.

[81]  J. Schlatterer,et al.  Xanthophylls in commercial egg yolks: quantification and identification by HPLC and LC-(APCI)MS using a C30 phase. , 2006, Journal of agricultural and food chemistry.

[82]  B. Chew,et al.  Carotenoid action on the immune response. , 2004, The Journal of nutrition.

[83]  B. J. Klevering,et al.  Risk alleles in CFH and ARMS2 are independently associated with systemic complement activation in age-related macular degeneration. , 2012, Ophthalmology.

[84]  M. W. Butler,et al.  Immune-system activation depletes retinal carotenoids in house finches (Carpodacus mexicanus) , 2010, Journal of Experimental Biology.

[85]  Paul V Garcia,et al.  Macular pigment and visual performance in glare: benefits for photostress recovery, disability glare, and visual discomfort. , 2011, Investigative ophthalmology & visual science.

[86]  Kazuhiko Yoshida,et al.  Inhibitory effects of lutein on endotoxin-induced uveitis in Lewis rats. , 2006, Investigative ophthalmology & visual science.

[87]  E. Harrison,et al.  Xanthophylls are preferentially taken up compared with beta-carotene by retinal cells via a SRBI-dependent mechanism. , 2008, Journal of lipid research.

[88]  R. Shanmugasundaram,et al.  Effects of dietary lutein and PUFA on PPAR and RXR isomer expression in chickens during an inflammatory response. , 2010, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[89]  S. Carpentier,et al.  Associations between Lutein, Zeaxanthin, and Age-Related Macular Degeneration: An Overview , 2009, Critical reviews in food science and nutrition.

[90]  B. Rosner,et al.  Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration. , 2010, Ophthalmology.

[91]  Hyeyoung Kim,et al.  β-Carotene and lutein inhibit hydrogen peroxide-induced activation of NF-κB and IL-8 expression in gastric epithelial AGS cells. , 2011, Journal of nutritional science and vitaminology.

[92]  B. Hammond,et al.  Macular Pigment and Visual Performance Under Glare Conditions , 2008, Optometry and vision science : official publication of the American Academy of Optometry.

[93]  Aaron Y. Lee,et al.  Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC) , 2010, Proceedings of the National Academy of Sciences.

[94]  D. Snodderly,et al.  Nutritional manipulation of primate retinas, III: Effects of lutein or zeaxanthin supplementation on adipose tissue and retina of xanthophyll-free monkeys. , 2005, Investigative ophthalmology & visual science.

[95]  J. Cruysberg,et al.  Subclinical changes in the juvenile crystalline macular dystrophy in Sjögren-Larsson syndrome detected by optical coherence tomography. , 2008, Ophthalmology.

[96]  F. Bairlein,et al.  Fat stores in a migratory bird: a reservoir of carotenoid pigments for times of need? , 2011, Journal of Comparative Physiology B.

[97]  Binxing Li,et al.  Purification and partial characterization of a lutein-binding protein from human retina. , 2009, Biochemistry.

[98]  A. Kijlstra,et al.  REVIEW ARTICLE, Immunological Factors in the Pathogenesis and Treatment of Age-Related Macular Degeneration , 2005, Ocular immunology and inflammation.

[99]  L. Pérez‐Rodríguez Carotenoids in evolutionary ecology: re‐evaluating the antioxidant role , 2009, BioEssays : news and reviews in molecular, cellular and developmental biology.

[100]  F. J. Romero,et al.  Lutein prevents cataract development and progression in diabetic rats , 2008, Graefe's Archive for Clinical and Experimental Ophthalmology.

[101]  T. Vliet,et al.  Effect of simultaneous, single oral doses of beta-carotene with lutein or lycopene on the beta-carotene and retinyl ester responses in the triacylglycerol-rich lipoprotein fraction of men. , 1998 .

[102]  N. Osborne,et al.  Retinal ischemia: mechanisms of damage and potential therapeutic strategies , 2004, Progress in Retinal and Eye Research.

[103]  A. Clifford,et al.  Maternal carotenoid status modifies the incorporation of dietary carotenoids into immune tissues of growing chickens (Gallus gallus domesticus). , 2003, The Journal of nutrition.

[104]  K. Yeum,et al.  Measurement of carotenoids, retinoids, and tocopherols in human lenses. , 1995, Investigative ophthalmology & visual science.

[105]  Laura A. Hecker,et al.  Genetic control of the alternative pathway of complement in humans and age-related macular degeneration. , 2010, Human molecular genetics.

[106]  J. Sangiovanni,et al.  Lutein and zeaxanthin protect photoreceptors from apoptosis induced by oxidative stress: relation with docosahexaenoic acid. , 2007, Investigative ophthalmology & visual science.

[107]  S. Connor,et al.  Competitive inhibition of carotenoid transport and tissue concentrations by high dose supplements of lutein, zeaxanthin and beta-carotene , 2010, European journal of nutrition.

[108]  R. Coletta,et al.  Impact of smoking on inflammation: overview of molecular mechanisms , 2011, Inflammation Research.

[109]  M. Failla,et al.  Xanthophylls and alpha-tocopherol decrease UVB-induced lipid peroxidation and stress signaling in human lens epithelial cells. , 2004, The Journal of nutrition.

[110]  S. Peters,et al.  Dietary lutein reduces ultraviolet radiation-induced inflammation and immunosuppression. , 2004, The Journal of investigative dermatology.

[111]  P. Davison,et al.  The impact of macular pigment augmentation on visual performance in normal subjects: COMPASS , 2011, Vision Research.

[112]  Da-You Zhao,et al.  Transformations of selected carotenoids in plasma, liver, and ocular tissues of humans and in nonprimate animal models. , 2002, Investigative ophthalmology & visual science.

[113]  P. Duell,et al.  The prime role of HDL to transport lutein into the retina: evidence from HDL-deficient WHAM chicks having a mutant ABCA1 transporter. , 2007, Investigative ophthalmology & visual science.

[114]  E. Chew,et al.  Nutritional supplementation in age-related macular degeneration , 2007, Current opinion in ophthalmology.

[115]  Justin A. Green,et al.  Lutein and zeaxanthin in eye and skin health. , 2009, Clinics in dermatology.

[116]  T. Berendschot,et al.  Macular pigment shows ringlike structures. , 2006, Investigative ophthalmology & visual science.

[117]  A. Stockman,et al.  Macular pigment densities derived from central and peripheral spectral sensitivity differences , 1998, Vision Research.

[118]  W. Stahl,et al.  Macular pigments lutein and zeaxanthin as blue light filters studied in liposomes. , 2001, Archives of biochemistry and biophysics.

[119]  P. Trumbo,et al.  Lutein and zeaxanthin intakes and risk of age-related macular degeneration and cataracts: an evaluation using the Food and Drug Administration's evidence-based review system for health claims. , 2006, The American journal of clinical nutrition.

[120]  U. Schmidt-Erfurth,et al.  Effects of lutein supplementation on macular pigment optical density and visual acuity in patients with age-related macular degeneration. , 2011, Investigative ophthalmology & visual science.

[121]  W. White,et al.  Intestinal absorption, serum clearance, and interactions between lutein and beta-carotene when administered to human adults in separate or combined oral doses. , 1995, The American journal of clinical nutrition.

[122]  L. Yonekura,et al.  Intestinal absorption of dietary carotenoids. , 2007, Molecular nutrition & food research.

[123]  S. Kritchevsky,et al.  Correlates of serum lutein + zeaxanthin: findings from the Third National Health and Nutrition Examination Survey. , 2004, The Journal of nutrition.

[124]  Binxing Li,et al.  Human ocular carotenoid-binding proteins , 2010, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[125]  S. Katayama,et al.  Apricot carotenoids possess potent anti-amyloidogenic activity in vitro. , 2011, Journal of agricultural and food chemistry.

[126]  F. Leckie,et al.  Parasites, testosterone and honest carotenoid-based signalling of health , 2007 .

[127]  R. Guymer,et al.  Perifoveal müller cell depletion in a case of macular telangiectasia type 2. , 2010, Ophthalmology.

[128]  S. Nilsson,et al.  Lipofuscin-formation in retinal pigment epithelial cells is reduced by antioxidants. , 2001, Free radical biology & medicine.

[129]  P. Barberger‐Gateau,et al.  Association of macular pigment density with plasma ω-3 fatty acids: the PIMAVOSA study. , 2012, Investigative ophthalmology & visual science.

[130]  H. Kwon,et al.  The non-provitamin A carotenoid, lutein, inhibits NF-kappaB-dependent gene expression through redox-based regulation of the phosphatidylinositol 3-kinase/PTEN/Akt and NF-kappaB-inducing kinase pathways: role of H(2)O(2) in NF-kappaB activation. , 2008, Free radical biology & medicine.

[131]  M. Fernández,et al.  Eggs distinctly modulate plasma carotenoid and lipoprotein subclasses in adult men following a carbohydrate-restricted diet. , 2010, The Journal of nutritional biochemistry.

[132]  D. Snodderly,et al.  Cigarette Smoking and Retinal Carotenoids: Implications for Age-related Macular Degeneration , 1996, Vision Research.

[133]  Paul S. Bernstein,et al.  Transport and retinal capture of lutein and zeaxanthin with reference to age-related macular degeneration. , 2008, Survey of ophthalmology.

[134]  X. Geng,et al.  Tubulins in the primate retina: evidence that xanthophylls may be endogenous ligands for the paclitaxel-binding site. , 2001, Bioorganic & medicinal chemistry.

[135]  R. Bone,et al.  Lutein, zeaxanthin, and the macular pigment. , 2001, Archives of biochemistry and biophysics.

[136]  Elizabeth J Johnson,et al.  Lutein bioavailability is higher from lutein-enriched eggs than from supplements and spinach in men. , 2004, The Journal of nutrition.

[137]  A. D. de Vos,et al.  Macrophages in the retina of normal Lewis rats and their dynamics after injection of lipopolysaccharide. , 1996, Investigative ophthalmology & visual science.

[138]  J. Hautvast,et al.  Dietary factors that affect the bioavailability of carotenoids. , 2000, The Journal of nutrition.

[139]  R. Bone,et al.  Analysis of the macular pigment by HPLC: retinal distribution and age study. , 1988, Investigative ophthalmology & visual science.