, Volume 36, Issue 9, pp 859–871 | Cite as

The role of docosahexaenoic acid in retinal function

  • Brett G. Jeffrey
  • Harrison S. Weisinger
  • Martha Neuringer
  • Drake C. Mitchell


An important role for docosahexaenoic acid (DHA) within the retina is suggested by its high levels and active conservation in this tissue. Animals raised on n-3-deficient diets have large reductions in retinal DHA levels that are associated with altered retinal function as assessed by the electroretinogram (ERG). Despite two decades of research in this field, little is known about the mechanisms underlying altered retinal function in n-3-deficient animals. The focus of this review is on recent research that has sought to elucidate the role of DHA in retinal function, particularly within the rod photoreceptor outer segments where DHA is found at its highest concentration. An overview is also given of human infant studies that have examined whether a neonatal dietary supply of DHA is required for the normal development of retinal function.



arachidonic acid


α-linolenic acid


docosahexaenoic acid


cGMP phosphodiesterase


eicosapentaenoic acid




isolated probe response


interphotoreceptor retinal binding proteins


interstimulus interval


long-chain polyunsaturated fatty acids




rod outer segment


retinal pigment epithelium


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  1. 1.
    Daemen, F.J. (1973) Vertebrate Rod Outer Segment Membranes, Biochim. Biophys. Acta 300, 255–288.PubMedGoogle Scholar
  2. 2.
    Fliesler, S.J., and Anderson, R.E. (1983) Chemistry and Metabolism of Lipids in the Vertebrate Retina, Prog. Lipid Res. 22, 79–131.PubMedCrossRefGoogle Scholar
  3. 3.
    Sprecher, H., Luthria, D.L., Mohammed, B.S., and Baykousheva, S.P. (1995) Reevaluation of the Pathways for the Biosynthesis of Polyunsaturated Fatty Acids, J. Lipid Res. 36, 2471–2477.PubMedGoogle Scholar
  4. 4.
    Anderson, R.E., O'Brien, P.J., Wiegand, R.D., Koutz, C.A., and Stinson, A.M. (1992) Conservation of Docosahexaenoic Acid in the Retina, Adv. Exp. Med. Biol. 318, 285–294.PubMedGoogle Scholar
  5. 5.
    Bazan, N.G., Gordon, W.C., and Rodriguez de Turco, E.B. (1992) Docosahexaenoic Acid Uptake and Metabolism in Photoreceptors: Retinal Conservation by an Efficient Retinal Pigment Epithelial Cell-Mediated Recycling Process, Adv. Exp. Med. Biol. 318, 295–306.PubMedGoogle Scholar
  6. 6.
    Stinson, A.M., Wiegand, R.D., and Anderson, R.E. (1991) Recycling of Docosahexaenoic Acid in Rat Retinas During n−3 Fatty Acid Deficiency, J. Lipid Res. 32, 2009–2017.PubMedGoogle Scholar
  7. 7.
    Neuringer, M. (1993) The Relationship of Fatty Acid Composition to Function in the Retina and Visual System, in Lipids, Learning, and the Brain: Fats in Infant Formulas, (Dobbing, J., ed.) pp. 134–163, Ross Laboratories, Columbus.Google Scholar
  8. 8.
    Tessier-Lavigne, M. (1991) Phototransduction and Information Processing in the Retina, in Principles of Neural Science, (Kandel, E.R., and Schwartz, J.H., eds.) pp. 400–418, Elsevier, New York.Google Scholar
  9. 9.
    Rodieck, R.W. (1998) The First Steps in Seeing, Sinauer Associates, Sunderland, MA.Google Scholar
  10. 10.
    Weisinger, H.S., Vingrys, A.J., and Sinclair, A.J. (1996) Electrodiagnostic Methods in Vision, Part 2. Origins of the Flash ERG, Clin. Exp. Optom. 79, 97–105.CrossRefGoogle Scholar
  11. 11.
    Jacobs, G.H. (1996) Primate Photopigments and Primate Color Vision, Proc. Natl. Acad. Sci. USA 93, 577–581.PubMedCrossRefGoogle Scholar
  12. 12.
    Stryer, L. (1986) Cyclic GMP Cascade of Vision, Annu. Rev. Neurosci. 9, 87–119.PubMedCrossRefGoogle Scholar
  13. 13.
    Heckenlively, J.R., and Arden, G.B. (1991) Principles and Practice of Clinical Electrophysiology of Vision, Mosby, New York.Google Scholar
  14. 14.
    Kriss, A., Jeffrey, B., and Taylor, D. (1992) The Electroretinogram in Infants and Young Children, J. Clin. Neurophysiol. 9, 373–393.PubMedCrossRefGoogle Scholar
  15. 15.
    Hood, D.C., and Birch, D.G. (1990) The a-Wave of the ERG as a Quantitative Measure of Human Receptor Activity, in Digest of Topical Meeting on Noninvasive Assessment of the Visual System, 1990, pp. 66–68, Optical Society of America, Washington.Google Scholar
  16. 16.
    Hood, D.C., and Birch, D.G. (1990) The a-Wave of the Human Electroretinogram and Rod Receptor Function, Invest. Ophthalmol. Vis. Sci. 31, 2070–2081.PubMedGoogle Scholar
  17. 17.
    Robson, J.G., and Frishman, L.J. (1995) Response Linearity and Kinetics of the Cat Retina: The Bipolar Cell Component of the Dark-Adapted Electroretinogram, Vis. Neurosci. 12, 837–850.PubMedCrossRefGoogle Scholar
  18. 18.
    Hood, D.C., and Birch, D.G. (1996) Beta Wave of the Scotopic (rod) Electroretinogram as a Measure of the Activity of Human ON-Bipolar Cells, J. Opt. Soc. Am. A 13, 623–633.Google Scholar
  19. 19.
    Sieving, P.A., Murayama, K., and Naarendorp, F. (1994) Push-Pull Model of the Primate Photopic Electroretinogram: A Role for Hyperpolarizing Neurons in Shaping the b-Wave, Vis. Neurosci. 11, 519–532.PubMedGoogle Scholar
  20. 20.
    Heynen, H., Wachtmeister, L., and van Norren, D. (1985) Origin of the Oscillatory Potentials in the Primate Retina, Vis. Res. 25, 1365–1373.PubMedCrossRefGoogle Scholar
  21. 21.
    Wyszecki, G., and Stiles, W.S. (1982) Color Science: Concepts and Methods, Quantitative Data and Formulae, John Wiley & Sons, New York.Google Scholar
  22. 22.
    Breton, M.E., Schueller, A.W., Lamb, T.D., and Pugh, E.N., Jr. (1994) Analysis of ERG a-Wave Amplification and Kinetics in Terms of the G-Protein Cascade of Phototransduction, Invest. Ophthalmol. Vis. Sci. 35, 295–309.PubMedGoogle Scholar
  23. 23.
    Birch, D.G., and Anderson, J.L. (1992) Standardized Full-Field Electroretinography. Normal Values and Their Variation with Age, Arch. Ophthalmol. 110, 1571–1576.PubMedGoogle Scholar
  24. 24.
    Fulton, A.B., and Rushton, W.A. (1978) The Human Rod ERG: Correlation with Psychophysical Responses in Light and Dark Adaptation, Vis. Res. 18, 793–800.PubMedCrossRefGoogle Scholar
  25. 25.
    Hood, D.C., and Birch, D.G. (1992) A Computational Model of the Amplitude and Implicit Time of the b-Wave of the Human ERG, Vis. Neurosci. 8, 107–126.PubMedGoogle Scholar
  26. 26.
    Fulton, A.B., and Hansen, R.M. (1988) Scotopic Stimulus/Response Relations of the b-Wave of the Electroretinogram, Doc. Ophthalmol. 68, 293–304.PubMedCrossRefGoogle Scholar
  27. 27.
    Birch, D.G., Birch, E.E., Hoffman, D.R., and Uauy, R.D. (1992) Retinal Development in Very-Low-Birth-Weight Infants Fed Diets Differing in Omega-3 Fatty Acids, Invest. Ophthalmol. Vis. Sci. 33, 2365–2376.PubMedGoogle Scholar
  28. 28.
    Robson, J.G., and Frishman, L.J. (1996) Photoreceptor and Bipolar Cell Contributions to the Cat Electroretinogram: A Kinetic Model for the Early Part of the Flash Response, J. Opt. Soc. Am. A 13, 613–622.Google Scholar
  29. 29.
    Lamb, T.D., and Pugh, E.N., Jr. (1992) A Quantitative Account of the Activation Steps Involved in Phototransduction in Amphibian Photoreceptors, J. Physiol. 449, 719–758.PubMedGoogle Scholar
  30. 30.
    Hood, D.C., and Birch, D.G. (1994) Rod Phototransduction in Retinitis Pigmentosa: Estimation and Interpretation of Parameters Derived from the Rod a-Wave, Invest. Ophthalmol. Vis. Sci. 35, 2948–2961.PubMedGoogle Scholar
  31. 31.
    Cideciyan, A.V., and Jacobson, S.G. (1996) An Alternative Phototransduction Model for Human Rod and Cone ERG a-Waves: Normal Parameters and Variation with Age, Vis. Res. 36, 2609–2621.PubMedCrossRefGoogle Scholar
  32. 32.
    Smith, N.P., and Lamb, T.D. (1997) The a-Wave of the Human Electroretinogram Recorded with a Minimally Invasive Technique, Vis. Res. 37, 2943–2952.PubMedCrossRefGoogle Scholar
  33. 33.
    Granit, R. (1933) The Components of the Retinal Action Potential in Mammals and Their Relation to the Discharge in the Optic Nerve, J. Physiol. 77, 207–239.PubMedGoogle Scholar
  34. 34.
    Granit, R. (1947) Sensory Mechanism of the Retina, Oxford University Press, London.Google Scholar
  35. 35.
    Birch, D.G., Hood, D.C., Nusinowitz, S., and Pepperberg, D.R. (1995) Abnormal Activation and Inactivation Mechanisms of Rod Transduction in Patients with Autosomal Dominant Retinitis Pigmentosa and the pro-23-his Mutation, Invest. Ophthalmol. Vis. Sci. 36, 1603–1614.PubMedGoogle Scholar
  36. 36.
    Hood, D.C., and Birch, D.G. (1993) Human Cone Receptor Activity: The Leading Edge of the a-Wave and Models of Receptor Activity, Vis. Neurosci. 10, 857–871.PubMedGoogle Scholar
  37. 37.
    Pepperberg, D.R., Birch, D.G., and Hood, D.C. (1997) Photoresponses of Human Rods in vivo Derived from Paired-Flash Electroretinograms, Vis. Neurosci. 14, 73–82.PubMedGoogle Scholar
  38. 38.
    Pepperberg, D.R., Birch, D.G., Hofmann, K.P., and Hood, D.C. (1996) Recovery Kinetics of Human Rod Phototransduction Inferred from the Two-Branched Alpha-Wave Saturation Function, J. Opt. Soc. Am. A 13, 586–600.Google Scholar
  39. 39.
    Salem, N., Jr., Kim, H.Y., and Yergey, J.A. (1986) Docosahexaenoic Acid: Membrane Function and Metabolism, in Heath Effects of Polyunsaturated Fatty Acids in Seafoods, (Simopoulos, A.P., Kifer, R.R., and Martin, R.E., eds.) pp. 263–317, Academic Press, Orlando.Google Scholar
  40. 40.
    Martinez, M., Ballabriga, A., and Gil-Gibernau, J.J. (1988) Lipids of the Developing Human Retina: I. Total Fatty Acids, Plasmalogens, and Fatty Acid Composition of Ethanolamine and Choline Phosphoglycerides, J. Neurosci. Res. 20, 484–490.PubMedCrossRefGoogle Scholar
  41. 41.
    Hrboticky, N., MacKinnon, M.J., and Innis, S.M. (1991) Retina Fatty Acid Composition of Piglets Fed from Birth with a Linoleic Acid-Rich Vegetable-Oil Formula for Infants, Am. J. Clin. Nutr. 53, 483–490.PubMedGoogle Scholar
  42. 42.
    Wiegand, R.D., Koutz, C.A., Stinson, A.M., and Anderson, R.E. (1991) Conservation of Docosahexaenoic Acid in Rod Outer Segments of Rat Retina During n−3 and n−6 Fatty Acid Deficiency, J. Neurochem. 57, 1690–1699.PubMedCrossRefGoogle Scholar
  43. 43.
    Gülcan, H.G., Alvarez, R.A., Maude, M.B., and Anderson, R.E. (1993) Lipids of Human Retina, Retinal Pigment Epithelium, and Bruch's Membrane/Choroid: Comparison of Macular and Peripheral Regions, Invest. Ophthalmol. Vis. Sci. 34, 3187–3193.PubMedGoogle Scholar
  44. 44.
    Makrides, M., Neumann, M.A., Byard, R.W., Simmer, K., and Gibson, R.A. (1994) Fatty Acid Composition of Brain, Retina, and Erythrocytes in Breast-and Formula-Fed Infants, Am. J. Clin. Nutr. 60, 189–194.PubMedGoogle Scholar
  45. 45.
    Salem, N., Jr. (1989) Omega-3 Fatty Acids: Molecular and Biochemical Aspects, in New Protective Roles for Selected Nutrients, pp. 109–228, Alan R. Liss, New York.Google Scholar
  46. 46.
    Benolken, R.M., Anderson, R.E., and Wheeler, T.G. (1973) Membrane Fatty Acids Associated with the Electrical Response in Visual Excitation, Science 182, 1253–1254.PubMedCrossRefGoogle Scholar
  47. 47.
    Bazan, H.E.P., Bazan, N.G., Feeney-Burns, L., and Berman, E.R. (1990) Lipids in Human Lipofuscin-Enriched Subcellular Fractions of Two Age Populations: Comparison with Rod Outer Segments and Neural Retina, Invest. Ophthalmol. Vis. Sci. 31, 1433–1443.PubMedGoogle Scholar
  48. 48.
    Lin, D.S., Anderson, G.J., Connor, W.E., and Neuringer, M. (1994) Effect of Dietary n−3 Fatty Acids upon the Phospholipid Molecular Species of the Monkey Retina, Invest. Ophthalmol. Vis. Sci. 35, 794–803.PubMedGoogle Scholar
  49. 49.
    Locke, K.G., Birch, E.E., Hoffman, D.R., Uauy, R., and Birch, D.G. (1998) Effect of Dietary DHA on Retinal Development in Healthy Full-Term Infants, Invest. Ophthalmol. Vis. Sci. 39, S829 (abstr.).Google Scholar
  50. 50.
    Neuringer, M., Fitzgerld, K.M., Weleber, R.G., Murphey, W.H., Giambrone, S.A., Cibis, G.W., and Arends, J. (1995) Electroretinograms in Four-Month-Old Full term Human Infants Fed Diets Differing in Long-Chain n−3 and n−6 Fatty Acids, Invest. Ophthalmol. Vis. Sci. 36, S48 (abstr.).Google Scholar
  51. 51.
    Faldella, G., Govoni, M., Alessandroni, R., Marchiani, E., Salvioli, G.P., Biagi, P.L., and Spanò, C. (1996) Visual Evoked Potentials and Dietary Long Chain Polyunsaturated Fatty Acids in Preterm Infants, Arch. Dis. Child Fetal Neonatal Ed. 75, F108-F112.PubMedGoogle Scholar
  52. 52.
    Lambert, S.R., Kriss, A., Taylor, D., Coffey, R., and Pembrey, M. (1989) Follow-up and Diagnostic Reappraisal of 75 Patients with Leber's Congenital Amaurosis, Am. J. Ophthalmol. 107, 624–631.PubMedGoogle Scholar
  53. 53.
    Hendrickson, A.E. (1993) Morphological Development of the Primate Retina, in Early Visual Development: Normal and Abnormal, (Simons, K., ed.) pp. 287–295, Oxford University Press, New York.Google Scholar
  54. 54.
    Blough, D.S., and Schrier, A.M. (1963) Scotopic Spectral Sensitivity in the Monkey, Science 139, 493–494.PubMedCrossRefGoogle Scholar
  55. 55.
    Harwerth, R.S., and Smith, E.L. (1985) Rhesus Monkey as a Model for Normal Vision of Humans, Am. J. Optom. Physiol. Opt. 62, 633–641.PubMedGoogle Scholar
  56. 56.
    Fulton, A., Hansen, R.M., Dorn, E., and Hendrickson, A. (1996) Development of Primate Rod Structure and Function, in Infant Vision. (Vital-Durand, F., Atkinson, J., and Braddick, O.J., eds.) pp. 33–49, Oxford University Press, New York.Google Scholar
  57. 57.
    Sheaff Greiner, R.C., Zhang, Q., Goodman, K.J., Giussani, D.A., Nathanielsz, P.W., and Brenna, J.T. (1996) Linoleate, Alpha-Linolenate, and Docosahexaenoate Recycling into Saturated and Monounsaturated Fatty Acids Is a Major Pathway in Pregnant or Lactating Adults and Fetal or Infant Rhesus Monkeys, J. Lipid Res. 37, 2675–2686.PubMedGoogle Scholar
  58. 58.
    Su, H.M., Bermardo, L., Mirmiran, M., Ma, X.H., Corso, T.N., Nathanielsz, P.W., and Brenna, J.T. (1999) Bioequivalence of Dietary Alpha-Linolenic and Docosahexaenoic Acids as Sources of Docosahexaenoate Accretion in Brain and Associated Organs of Neonatal Baboons, Pediatr. Res. 45, 87–93.PubMedGoogle Scholar
  59. 59.
    Sheaff Greiner, R.C., Winter, J., Nathanielsz, P.W., and Brenna, J.T. (1997) Brain Docosahexaenoate Accretion in Fetal Baboons: Bioequivalence of Dietary Alpha-Linolenic and Docosahexaenoic Acids, Pediatr. Res. 42, 826–834.Google Scholar
  60. 60.
    Connor, W.E., Neuringer, M., and Lin, D.S. (1990) Dietary Effects on Brain Fatty Acid Composition: The Reversibility of n−3 Fatty Acid Deficiency and Turnover of Docosahexaenoic Acid in the Brain, Erythrocytes, and Plasma of Rhesus Monkeys, J. Lipid Res. 31, 237–247.PubMedGoogle Scholar
  61. 61.
    Boothe, R.G., Dobson, V., and Teller, D.Y. (1985) Postnatal Development of Vision in Human and Nonhuman Primates, Annu. Rev. Neurosci. 8, 495–545.PubMedCrossRefGoogle Scholar
  62. 62.
    Jeffrey, B.G. (2000) The Role of Docosahexaenoic Acid in Retinal Function of the Rhesus Monkey (Macaca mulatta), Ph.D. Thesis, The Flinders University of South Australia, Adelaide, Australia, pp. 126–186.Google Scholar
  63. 63.
    Carnielli, V.P., Wattimena, D.J.L., Luijendijk, I.H.T., Boerlage, A., Degenhart, H.J., and Sauer, P.J.J. (1996) The Very Low Birth Weight Premature Infant Is Capable of Synthesizing Arachidonic and Docosahexaenoic Acids from Linoleic and Linolenic Acids, Pediatr. Res. 40, 169–174.PubMedGoogle Scholar
  64. 64.
    Salem, N., Jr., Wegher, B., Mena, P., and Uauy, R. (1996) Arachidonic and Docosahexaenoic Acids Are Biosynthesized from Their 18-Carbon Precursors in Human Infants, Proc. Natl. Acad. Sci. USA 93, 49–54.PubMedCrossRefGoogle Scholar
  65. 65.
    Wheeler, T.G., Benolken, R.M., and Anderson, R.E. (1975) Visual Membranes: Specificity of Fatty Acid Precursors for the Electrical Response to Illumination, Science 188, 1312–1314.PubMedCrossRefGoogle Scholar
  66. 66.
    Watanabe, I., Kato, M., Aonuma, H., Hashimoto, A., Naito, Y., Moriuchi, A., and Okuyama, H. (1987) Effect of Dietary Alpha-Linolenate/Linoleate Balance on the Lipid Composition and Electroretinographic Responses in Rats, Adv. Biosci. 62, 563–570.Google Scholar
  67. 67.
    Bourre, J.-M., Francois, M., Youyou, A., Dumont, O., Piciotti, M., Pascal, G., and Durand, G. (1989) The Effects of Dietary α-Linolenic Acid on the Composition of Nerve Membranes. Enzymatic Activity, Amplitude of Electrophysiological Parameters. Resistance to Poisons and Performance of Learning Tasks in Rats, J. Nutr. 119, 1880–1892.PubMedGoogle Scholar
  68. 68.
    Weisinger, H.S., Vingrys, A.J., and Sinclair, A.J. (1996) Effect of Dietary n−3 Deficiency on the Electroretinogram in the Guinea Pig, Ann. Nutr. Metab. 40, 91–98.PubMedGoogle Scholar
  69. 69.
    Weisinger, H.S., Vingrys, A.J., and Sinclair, A.J. (1995) Dietary Manipulation of Long-Chain Polyunsaturated Fatty Acids in the Retina and Brain of Guinea Pigs, Lipids 30, 471–473.PubMedGoogle Scholar
  70. 70.
    Weisinger, H.S., Vingrys, A.J., Bui, B.V., and Sinclair, A.J. (1999) Effects of Dietary n−3 Fatty Acid Deficiency and Repletion in the Guinea Pig Retina, Invest. Ophthalmol. Vis. Sci. 40, 327–338.PubMedGoogle Scholar
  71. 71.
    Armitage, J.A., Weisinger, H.S., Vingrys, A.J., and Sinclair, A.J. (2000) Perinatal Omega-3 Fatty Acid Deficiency Alters ERG in Adult Rats Irrespective of Tissue Fatty Acid Content, Invest. Ophthalmol. Vis. Sci. 41, S245 (abstr.).Google Scholar
  72. 72.
    Bush, R.A., Malnoe, A., Reme, C.E., and Williams, T.P. (1994) Dietary Deficiency of n−3 Fatty Acids Alters Rhodopsin Content and Function in the Rat Retina, Invest. Ophthalmol. Vis. Sci. 35, 91–100.PubMedGoogle Scholar
  73. 73.
    Bush, R.A., Reme, C.E., and Malnoe, A. (1991) Light Damage in the Rat Retina: The Effect of Dietary Deprivation of n−3 Fatty Acids on Acute Structural Alterations, Exp. Eye Res. 53, 741–752.PubMedCrossRefGoogle Scholar
  74. 74.
    Reme, C.F., Malnoe, A., Jung, H.H., Wei, J.Q., and Munz, K. (1994) Effect of Dietary Fish Oil on Acute Light Induced Photoreceptor Damage in the Rat Retina, Invest. Ophthalmol. Vis. Sci. 35, 78–90.PubMedGoogle Scholar
  75. 75.
    Wiedmann, T.S., Pates, R.D., Beach, J.M., Salmon, A., and Brown, M.F. (1988) Lipid-Protein Interactions Mediate the Photochemical Function of Rhodopsin, Biochemistry 27, 6469–6474.PubMedCrossRefGoogle Scholar
  76. 76.
    Brown, M.F. (1994) Modulation of Rhodopsin Function by Properties of the Membrane Bilayer, Chem. Phys. Lipids 73, 159–180.PubMedCrossRefGoogle Scholar
  77. 77.
    Litman, B.J., and Mitchell, D.C. (1996) A Role for Phospholipid Polyunsaturation in Modulating Membrane Protein Function, Lipids 31 (Suppl.), S193-S197.PubMedGoogle Scholar
  78. 78.
    Pugh, E.N., Jr., Nikonov, S., and Lamb, T.D. (1999) Molecular Mechanisms of Vertebrate Photoreceptor Light Adaptation, Curr. Opin. Neurobiol. 9, 410–418.PubMedCrossRefGoogle Scholar
  79. 79.
    Christensen, M.M., Lund, S.P., Simonsen, L., Hass, U., Simonsen, S.E., and Høy, C.-E. (1998) Dietary Structured Tracylglycerols Containing Docosahexaenoic Acid Given from Birth Affect Visual and Auditory Performance and Tissue Fatty Acid Profiles in Rats, J. Nutr. 128, 1011–1017.PubMedGoogle Scholar
  80. 80.
    Mitchell, D.C., Straume, M., and Litman, B.J. (1992) Role of sn-1-Saturated, sn-2-Polyunsaturated Phospholipids in Control of Membrane Receptor Conformational Equilibrium: Effects of Cholesterol and Acyl Chain Unsaturation on the Metarhodopsin I in Equilibrium with Metarhodopsin II Equilibrium, Biochemistry 31, 662–670.PubMedCrossRefGoogle Scholar
  81. 81.
    Pawlosky, R.J., Denkins, Y., Ward, G., and Salem, N., Jr. (1997) Retinal and Brain Accretion of Long-Chain Polyunsaturated Fatty Acids in Developing Felines: The Effects of Corn Oil-Based Maternal Diets, Am. J. Clin. Nutr. 65, 465–472.PubMedGoogle Scholar
  82. 82.
    Neuringer, M., Connor, W.E., Van Petten, C., and Barstad, L. (1984) Dietary Omega-3 Fatty Acid Deficiency and Visual Loss in Infant Rhesus Monkeys, J. Clin. Investig. 73, 272–276.PubMedCrossRefGoogle Scholar
  83. 83.
    Neuringer, M., Connor, W.E., Lin, D.S., Barstad, L., and Luck, S. (1986) Biochemical and Functional Effects of Prenatal and Postnatal Omega-3 Fatty Acid Deficiency on Retina and Brain in Rhesus Monkeys, Proc. Natl. Acad. Sci. USA 83, 4021–4025.PubMedCrossRefGoogle Scholar
  84. 84.
    Neuringer, M., Connor, W.E., Lin, D.S., Anderson, G.J., and Barstad, L. (1991) Dietary Omega-3 Fatty Acids: Effects on Retinal Lipid Composition and Function in Primates, in Retinal Degenerations, (Anderson, R.E., Hollyfield, J.G., and La Vail, M.M., eds.) pp. 1–13, CRC Press, New York.Google Scholar
  85. 85.
    Neuringer, M., Connor, W.E., Anderson, G.J., and Teemer, C.D. (1997) Effects of Dietary Linolenic Acid (18∶3n−3) and DHA (22∶6n−3) on Electroretinogram Post-Flash Recovery in Rhesus Monkey Infants, Investig. Ophthalmol. Vis. Sci. S747 (abstr.)Google Scholar
  86. 86.
    Neuringer, M., Jeffrey, B.G., and Gibson, R.A. (2000) n−3 Fatty Acid Deficiency Alters Rod Phototransduction and Recovery, Invest. Ophthalmol. Vis. Sci. 41, S493 (abstr.).Google Scholar
  87. 87.
    Mitchell, D.C., Niu, S.L., and Litman, B.J. (2001) Optimization of Receptor-G Protein Coupling by Bilayer Lipid Composition I: Kinetics of Rhodopsin-Transducin Binding, J. Biol. Chem., in press.Google Scholar
  88. 88.
    Koutalos, Y., and Yau, K.W. (1996) Regulation of Sensitivity in Vertebrate Rod Photoreceptors by Calcium, Trends Neurosci. 19, 73–81.PubMedCrossRefGoogle Scholar
  89. 89.
    Vreugdenhil, M., Bruehl, C., Voskuyl, R.A., Kang, J., Leaf, A., and Wadman, W.J. (1996) Polyunsaturated Fatty Acids Modulate Sodium and Calcium Currents in CA1 Neurons, Proc. Natl. Acad. Sci. USA 93, 12559–12563.PubMedCrossRefGoogle Scholar
  90. 90.
    Leaf, A. (1995) Omega-3 Fatty Acids and Prevention of Ventricular Fibrillation, Prostaglandins Leukotrienes Essent. Fatty Acids 52, 197–198.CrossRefGoogle Scholar
  91. 91.
    Huang, J., Wyse, J.P., and Spira, A.W. (1990) Ontogenesis of the Electroretinogram in a Precocial Mammal, the Guinea Pig (Cavia porcellus), J. Comp. Biochem. Physiol. 95A, 149–155.CrossRefGoogle Scholar
  92. 92.
    Wikler, K.C., Williams, R.W., and Rakic, P. (1990) Photoreceptor Mosaic: Number and Distribution of Rods and Cones in the Rhesus Monkey Retina, J. Comp. Neurol. 297, 499–508.PubMedCrossRefGoogle Scholar
  93. 93.
    Bone, B.A., Landrum, J.T., Hime, G.W., Cains, A., and Zamor, J. (1993) Stereochemistry of the Human Macular Carotenoids, Invest. Ophthamol. Vis. Sci. 34, 2033–2040.Google Scholar
  94. 94.
    Wikler, K.C., and Rakic, P. (1990) Distribution of Photoreceptor Subtypes in the Retina of Diurnal and Nocturnal Primates, J. Neurosci. 10, 3390–3401.PubMedGoogle Scholar
  95. 95.
    Dorn, E.M., Hendrickson, L., and Hendrickson, A.E. (1995) The Appearance of Rod Opsin During Monkey Retinal Development, Invest. Ophthalmol. Vis. Sci. 36, 2634–2651.PubMedGoogle Scholar
  96. 96.
    Neuringer, M., and Connor, W.E. (1990) Supplementation with Dpcosahexaenoic Acid (22∶6ω−3) Fails to Correct Electroretinogram Abnormalities Produced by Omega-3 Fatty Acid Deficiency in Rhesus Monkeys, Invest. Ophthalmol, Vis. Sci. 31, 426 (abstr.).Google Scholar
  97. 97.
    Bui, B.V., and Vingrys, A.J. (1999) Postnatal Development of Receptoral Responses in Pigmented and Albino Guinea Pigs (Cavia porcellus), Invest. Ophthalmol. Vis. Sci. 40, S22 (abstr.).Google Scholar
  98. 98.
    Bazan, N.G., Reddy, T.S., Redmond, T.M., Wiggert, B., and Chader, G.J. (1985) Endogenous Fatty Acids Are Covalently and Noncovalently Bound to Interphotoreceptor Retinoid-Binding Protein in the Monkey Retina, J. Biol. Chem. 260, 13677–13680.PubMedGoogle Scholar
  99. 99.
    Chen, Y., Saari, J.C., and Noy, N. (1993) Interactions of all-trans-Retinol and Long-Chain Fatty Acids with Interphotoreceptor Retinoid-Binding Protein, Biochemistry 32, 11311–11318.PubMedCrossRefGoogle Scholar
  100. 100.
    Chen, Y., Houghton, L.A., Brenna, J.T., and Noy, N. (1996) Docosahexaenoic Acid Modulates the Interactions of the Interphotoreceptor Retinoid-Binding Protein with 11-cis-Retinal, J. Biol. Chem. 271, 20507–20515.PubMedCrossRefGoogle Scholar
  101. 101.
    Farquharson, J., Jamieson, E.C., Abbasi, K.A., Patrick, W.J.A., Logan, R.W., and Cockburn, F. (1995) Effect of Diet on the Fatty Acid Composition of the Major Phospholipids of Infant Cerebral Cortex, Arch. Dis. Child. 72, 198–203.PubMedCrossRefGoogle Scholar
  102. 102.
    Yau, K.W. (1994) Phototransduction Mechanism in Retinal Rods and Cones. The Friedenwald Lecture, Invest. Opthalmol. Vis. Sci. 5, 9–32.Google Scholar
  103. 103.
    Cotman, C., Blank, M.L., Moehl, A., and Snyder, F. (1969) Lipid Composition of Synaptic Plasma Membranes Isolated from Rat Brain by Zonal Centrifugation, Biochemistry 8, 4606–4612.PubMedCrossRefGoogle Scholar
  104. 104.
    Sun, G.Y., and Sun, Y. (1972) Phospholipids and Acyl Groups of Synaptosomal and Myelin Membranes Isolated from the Cerebral Cortex of Squirrel Monkey (Saimiri sciureus), Biochim. Biophys. Acta 280, 306–315.PubMedGoogle Scholar
  105. 105.
    Kandel, E.R., and Schwartz, J.H. (1991) Principles of Neural Science, Elsevier, New York.Google Scholar

Copyright information

© AOCS Press 2001

Authors and Affiliations

  • Brett G. Jeffrey
    • 1
    • 3
  • Harrison S. Weisinger
    • 2
    • 4
  • Martha Neuringer
    • 3
  • Drake C. Mitchell
    • 4
  1. 1.Department of Paediatrics and Child Health, Flinders Medical CentreThe Flinders University of South AustraliaBedford ParkAustralia
  2. 2.Department of Food ScienceRoyal Melbourne Institute of Technology UniversityMelbourneAustralia
  3. 3.Oregon Regional Primate Research CenterOregon Health and Science UniversityPorland
  4. 4.Laboratory of Membrane Biochemistry and BiophysicsNational Institute on Alcohol Abuse and Alcoholism, National Institutes of HealthBethesda

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