Skip to main content
SpringerLink
Log in

Visual acuity and retinal function in infant monkeys fed long-chain PUFA

  • Articles
  • Published:
Lipids

Abstract

Previous randomized clinical trials suggest that supplementation of the human infant diet with up to 0.35% DHA may benefit visual development. The aim of the current study was to assess the impact of including arachidonic acid (AA) and a higher level of DHA in the postnatal monkey diet on visual development. Infant rhesus monkeys were fed either a control diet (2.0% α-linolenic acid as the sole n−3 FA) or a supplemented diet (1.0% DHA and 1.0% AA) from birth. Visual evoked potential acuity was measured at 3 mon of age. Rod and cone function were assessed in terms of parameters describing phototransduction. Electroretinogram (ERG) amplitudes and implicit times were recorded over a wide intensity range (−2.2 to 4.0 log scot td-sec) and assessed in terms of intensity response functions. Plasma DHA and AA were significantly increased (P <0.001) in the diet-supplemented monkeys compared with the control monkeys. There was an approximately equal effect of diet for the rod phototransduction parameters, sensitivity, and capacitance but in the opposite directions. Diet-supplemented monkeys had significantly shorter b-wave implicit times at low retinal illuminances (<−0.6 log scot td-sec). There were no significant effects of diet for visual acuity or the other 23 ERG parameters measured. The results suggest that supplementation of the infant monkey diet with 1.0% DHA and 1.0% AA neither harms nor provides substantial benefit to the development of visual acuity or retinal function in the first four postnatal months.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

AA, 20∶4n−6:

arachidonic acid

ALA, 18∶3n−3:

α-linolenic acid

ERG:

electroretinogram

LCPUFA:

long-chain PUFA

OP:

oscillatory potentials

P2:

postreceptoral response

P3:

phototransduction response

PCA:

postconceptual age

VEP:

visual evoked potential

References

  1. 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.

    PubMed  CAS  Google Scholar 

  2. Birch, E.E., Birch, D.G., Hoffman, D.R, and Uauy, R. (1992) Dietary Essential Fatty Acid Supply and Visual Acuity Development, Invest. Ophthalmol. Vis. Sci. 32, 3242–3253.

    Google Scholar 

  3. Carlson, S.E., Werkman, S.H., Rhodes, P.G., and Tolley, E.A. (1993) Visual-Acuity Development in Healthy Preterm Infants, Effect of Marine-Oil Supplementation, Am. J. Clin. Nutr. 58, 35–42.

    PubMed  CAS  Google Scholar 

  4. Makrides, M., Neumann, M., Simmer, K., Pater, J., and Gibson, R. (1995) Are Long-Chain Polyunsaturated Fatty Acids Essential Nutrients in Infancy?, Lancet 345, 1463–1468.

    Article  PubMed  CAS  Google Scholar 

  5. Carlson, S.E., Ford, A.J., Werkman, S.H., Peeples, J.M., and Koo, W.W.K. (1996) Visual Acuity and Fatty Acid Status of Term Infants Fed Human Milk and Formulas With and Without Docosahexaenoate and Arachidonate from Egg Yolk Lecithin, Pediatr. Res. 39, 882–888.

    PubMed  CAS  Google Scholar 

  6. Carlson, S.E., Werkman, S.H., and Tolley, E.A. (1996) Effect of Long-Chain n−3 Fatty Acid Supplementation on Visual Acuity and Growth of Preterm Infants With and Wihtout Bronchopulmonary Dysplasia, Am. J. Clin. Nutr. 63, 687–697.

    PubMed  CAS  Google Scholar 

  7. Auestad, N., Montalto, M.B., Hall, R.T., Fitzgerald, K.M., Wheeler, R.E., Connor, W.E., Neuringer, M., Connor, S.L., Taylor, J.A., and Hartmann, E.E. (1997) Visual Acuity, Erythrocyte Fatty Acid Composition, and Growth in Term Infants Fed Formulas with Long Chain Polyunsaturated Fatty Acids for One Year, Pediatr. Res. 41, 1–10.

    PubMed  CAS  Google Scholar 

  8. Birch, E.E., Hoffman, D.R., Uauy, R., Birch, D.G., and Prestidge, C. (1998) Visual Acuity and the Essentiality of Docosahexaenoic Acid and Arachidonic Acid in the Diet of Term Infants, Pediatr. Res. 44, 201–209.

    PubMed  CAS  Google Scholar 

  9. Jorgensen, M.H., Holmer, G., Lund, P., Hernell, O., and Michaelsen, K.F. (1998) Effect of Formula Supplemented with Docosahexaenoic Acid and γ-Linolenic Acid on Fatty Acid Status and Visual Acuity in Term Infants, J. Pediatr. Gastroenterol. Nutr. 26, 412–421.

    Article  CAS  Google Scholar 

  10. Hoffman, D.R., Birch, E.E., Birch, D.G., Uauy, R., Castaneda, Y.S., Lapus, M.G., and Wheaton, D.H. (2000) Impact of Early Dietary Intake and Blood Lipid Composition of Long-Chain Polyunsaturated Fatty Acids on Later Visual Development, J. Pediatr. Gastroenterol. Nutr. 31, 540–553.

    PubMed  CAS  Google Scholar 

  11. Makrides, M., Neumann, M.A., Simmer, K., and Gibson, R.A. (2000) A Critical Appraisal of the Role of Dietary Long-Chain Polyunsaturated Fatty Acids on Neural Indices of Term Infants: A Randomized, Controlled Trial, Pediatrics 105, 32–38.

    Article  PubMed  CAS  Google Scholar 

  12. Auestad, N., Halter, R., Hall, R.T., Blatter, M., Bogle, M.L., Burks, W., Erickson, J.R., Fitzgerald, K.M., Dobson, V., Innis, S.M., et al. (2001) Growth and Development in Term Infants Fed Long-Chain Polyunsaturated Fatty Acids: A Double-Masked, Randomized, Parallel, Prospective, Multivariate Study, Pediatrics 108, 372–381.

    Article  PubMed  CAS  Google Scholar 

  13. O’Connor, D.L., Hall, R., Adamkin, D., Auestad, N., Castillo, M., Connor, W.E., Connor, S.L., Fitzgerald, K., Groh-Wargo, S., Hartmann, E.E., et al. (2001) Growth and Development in Preterm Infants Fed Long-Chain Polyunsaturated Fatty Acids: A Prospective, Randomized Controlled Trial, Pediatrics 108, 359–371.

    Article  PubMed  CAS  Google Scholar 

  14. Birch, E.E., Hoffman, D.R., Castaneda, Y.S., Fawcett, S.L., Birch, D.G., and Uauy, R.D. (2002) A Randomized Controlled Trial of Long-Chain Polyunsaturated Fatty Acid Supplementation of Formula in Term Infants After Weaning at 6 Weeks of Age, Am. J. Clin. Nutr. 75, 570–580.

    PubMed  CAS  Google Scholar 

  15. Hamosh, M., and Salem, N., Jr. (1998) Long-Chain Polyunsaturated Fatty Acids, Biol. Neonate 74, 106–120.

    Article  PubMed  CAS  Google Scholar 

  16. Jensen, R.G. (1999) Lipids in Human Milk, Lipids 34, 1243–1271.

    Article  PubMed  CAS  Google Scholar 

  17. Weisinger, H.S., Vingrys, A.J., and Sinclair, A.J. (1996) The Effect of Docosahexaenoic Acid on the Electroretinogram of the Guinea Pig, Lipids 31, 65–70.

    Article  PubMed  CAS  Google Scholar 

  18. 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.

    PubMed  CAS  Google Scholar 

  19. Jeffrey, B.G., Mitchell, D.C., Gibson, R.A., and Neuringer, M. (2002) n−3 Fatty Acid Deficiency Alters Recovery of the Rod Photoresponse in Rhesus Monkeys, Invest. Ophthalmol. Vis. Sci. 43, 2806–2814.

    PubMed  Google Scholar 

  20. Jacobs, G.H. (1996) Primate Photopigments and Primate Color Vision, Proc. Natl. Acad. Sci. USA 93, 577–581.

    Article  PubMed  CAS  Google Scholar 

  21. Blough, D.S., and Schrier, A.M. (1963) Scotopic Spectral Sensitivity in the Monkey, Science 139, 493–494.

    Article  PubMed  CAS  Google Scholar 

  22. 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.

    PubMed  CAS  Google Scholar 

  23. 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, Oxford.

    Google Scholar 

  24. Fulton, A., Hansen, R.M., Dorn, E., and Hendrickson, A. (1996) Development of Primate Rod Structure and Function, in Infant Vision (Vital-Durand, F., ed.), pp. 33–49, Oxford University Press, New York.

    Google Scholar 

  25. Salem, N., Jr., Reyzer, M., and Karanian, J. (1996) Losses of Arachidonic Acid in Rat Liver After Alcohol Inhalation, Lipids 31 (Suppl.), S153-S156.

    PubMed  CAS  Google Scholar 

  26. Victor, J.D., and Mast, J. (1991) A New Statistic for Steady-State Evoked Potentials, Electroencephalogr. Clin. Neurophysiol. 78, 378–388 [published erratum appears in Electroencephalogr. Clin. Neurophysiol. 83, 270, 1992].

    Article  PubMed  CAS  Google Scholar 

  27. Norcia, A.M., and Tyler, C.W. (1985) Spatial Frequency Sweep VEP: Visual Acuity During the First Year of Life, Vision Res. 25, 1399–1408.

    Article  PubMed  CAS  Google Scholar 

  28. Massof, R.W., Wu, L., Finkelstein, D., Perry, C., Starr, S.J., and Johnson, M.A. (1984) Properties of Electroretinographic Intensity-Response Functions in Retinitis Pigmentosa, Doc. Ophthalmol. 57, 279–296.

    Article  PubMed  CAS  Google Scholar 

  29. Hansen, R.M., and Fulton, A.B. (1993) Development of Scotopic Retinal Sensitivity, in Early Visual Development Normal and Abnormal (Simons, K., ed.), pp. 130–142, Oxford University Press, Oxford.

    Google Scholar 

  30. 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.

    PubMed  CAS  Google Scholar 

  31. 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.

    PubMed  CAS  Google Scholar 

  32. Lamb, T.D., and Pugh, E.N., Jr. (1992) A Quantitative Account of the Activation Steps Involved in Phototransduction in Amphibian Photoreceptors, J. Physiol. (London) 449, 719–758.

    CAS  Google Scholar 

  33. 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.

    PubMed  CAS  Google Scholar 

  34. 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.

    PubMed  CAS  Google Scholar 

  35. 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.

    Article  PubMed  CAS  Google Scholar 

  36. Hood, D.C., and Birch, D.G. (1997) Assessing Abnormal Rod Photoreceptor Activity with the a-Wave of the ERG: Applications and Methods, Doc. Ophthalmol. 92, 253–267.

    CAS  Google Scholar 

  37. Smith, N.P., and Lamb, T.D. (1997) The a-Wave of the Human Electroretinogram Recorded with a Minimally Invasive Technique, Vision Res. 37, 2943–2952.

    Article  PubMed  CAS  Google Scholar 

  38. 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.

    PubMed  CAS  Google Scholar 

  39. Johnson, M.L., and Frasier, S.G. (1985) Nonlinear Least Squares Analysis, Methods Enzymol. 117, 301–342.

    CAS  Google Scholar 

  40. Johnson, M.L., and Faunt, L.M. (1992) Parameters Estimation by Least-Squares Methods, Methods Enzymol. 210, 1–37.

    Article  PubMed  CAS  Google Scholar 

  41. 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. 86–90.

    Google Scholar 

  42. Champoux, M., Hibbeln, J.R., Shannon, C., Majchrzak, S., Suomi, S.J., Salem, N., Jr., and Higley, J.D. (2002) Fatty Acid Formula Supplementation and Neuromotor Development in Rhesus Monkey Neonates, Pediatr. Res. 51, 273–281.

    PubMed  CAS  Google Scholar 

  43. Sieving, P.A., Frishman, L.J., and Steinberg, R.H. (1986) Scotopic Threshold Response of Proximal Retina in Cat, J. Neurophysiol. 56, 1048–1061.

    Google Scholar 

  44. 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.

    Article  CAS  Google Scholar 

  45. Karwoski, C., and Karwoski, K. (1991) Oscillatory Potentials, in Principles and Practice of Clinical Electrophysiology of Vision (Heckenlively, J.R., ed.), pp. 125–128, Mosby, New York.

    Google Scholar 

  46. Neuringer, M., Connor, W.E., Lin, D.S., Anderson, G.J., and Barstad, L. (1991) Dietary ω-3 Fatty Acids: Effects on Retinal Lipid Composition and Function in Primates, in Retinal Degenerations (R.E. Anderson, ed.), pp. 1–13, CRC Press, Boca Raton.

    Google Scholar 

  47. Lands, W.E.M., Morris, A., and Libelt, B. (1990) Quantitative Effects of Dietary Polyunsaturated Fats on the Composition of Fatty Acids in Rat Tissues, Lipids 25, 505–516.

    PubMed  CAS  Google Scholar 

  48. Koutz, C.A., Wiegand, R.D., Rapp, L.M., and Anderson, R.E. (1995) Effect of Dietary Fat on the Response of the Rat Retina to Chronic and Acute Light Stress, Exp. Eye Res. 60, 307–316.

    Article  PubMed  CAS  Google Scholar 

  49. Jeffrey, B.G., Weisinger, H.S., Neuringer, M., and Mitchell, D.C. (2001) The Role of Docosahexaenoic Acid in Retinal Function, Lipids 36, 859–871.

    PubMed  CAS  Google Scholar 

  50. 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.

    PubMed  CAS  Google Scholar 

  51. Martinez, M. (1992) Tissue Levels of Polyunsaturated Fatty Acids During Early Human Development, J. Pediatr. 120, S129-S138.

    Article  PubMed  CAS  Google Scholar 

  52. Hoffman, D.R., and Uauy, R. (1992) Essentiality of Dietary Omega-3 Fatty Acids for Premature Infants: Plasma and Red Blood Cell Fatty Acid Composition, Lipids 27, 886–895.

    PubMed  CAS  Google Scholar 

  53. 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.

    PubMed  CAS  Google Scholar 

  54. Riesbick, S., Neuringer, M., and Connor, W.E. (1996) Effects of Omega-3 Fatty Acid Deficiency in Nonhuman Primates, in Recent Developments in Infant Nutrition (Bindels, J.G., ed.) pp. 157–172, Kluwer, Dordrecht.

    Google Scholar 

  55. 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.

    PubMed  CAS  Google Scholar 

  56. 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.

    Article  PubMed  CAS  Google Scholar 

  57. Sheaff Greiner, R.C., Zhang, Q., Goodman, K.J., Giussani, D.A., Nathanielsz, P.W., and Brenna, J.T. (1996) Linoleate, α-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. Lipids Res. 37, 2675–2686.

    CAS  Google Scholar 

  58. Sheaff Greiner, R.C., Winter, J., Nathanielsz, P.W., and Brenna, J.T. (1997) Brain Docosahexaenoate Accretion in Fetal Baboons: Bioequivalence of Dietary α-Linolenic and Docosahexaenoic Acids, Pediatr Res. 42, 826–834.

    Google Scholar 

  59. Su, H.M., Bernardo, L., Mirmiran, M., Ma, X.H., Corso, T.N., Nathanielsz, P.W., and Brenna, J.T. (1999) Bioequivalence of Dietary α-Linolenic and Docosahexaenoic Acids as Sources of Docosahexaenoate Accretion in Brain and Associated Organs of Neonatal Baboons, Pediatr Res. 45, 87–93.

    PubMed  CAS  Google Scholar 

  60. 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.

    PubMed  CAS  Google Scholar 

  61. 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.

    PubMed  CAS  Google Scholar 

  62. 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.

    PubMed  CAS  Google Scholar 

  63. Teller, D.Y., and Boothe, R.G. (1979) The Development of Vision in Infant Primates, Trans. Ophthalmol. Soc. UK 99, 333–337.

    PubMed  CAS  Google Scholar 

  64. Carlson, S.E. (1996) Arachidonic Acid Status of Human Infants: Influence of Gestational Age at Birth and Diets with Very Long Chain n−3 and n−6 Fatty Acids, J. Nutr. 126, 1092S-1098S.

    PubMed  CAS  Google Scholar 

  65. Craig Schmidt, M.C., Stieh, K.E., and Lien, E.L. (1996) Retinal Fatty Acids of Piglets Fed Docosahexaenoic and Arachidonic Acids from Microbial Sources, Lipids 31, 53–59.

    Article  PubMed  CAS  Google Scholar 

  66. Jiménez, J., Boza, J., Suárez, M.D., and Gil, A. (1997) The Effect of a Formula Supplemented with n−3 and n−6 Long-Chain Polyunsaturated Fatty Acids on Plasma Phospholipid, Liver Microsomal, Retinal, and Brain Fatty Acid Composition in Neonatal Piglets, J. Nutr. Biochem. 8, 217–223.

    Article  Google Scholar 

  67. Alessandri, J.M., Goustard, B., Guesnet, P., and Durand, A. (1998) Docosahexaenoic Acid Concentrations in Retinal Phospholipids of Piglets Fed an Infant Formula Enriched with Long-Chain Polyunsaturated Fatty Acids: Effects of Egg Phospholipids and Fish Oils with Different Ratios of Eicosapentaenoic Acid to Docosahexaenoic Acid, Am. J. Clin. Nutr. 67, 377–385.

    PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Brett G. Jeffrey

    Present address: Department of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, 97006, Beaverton, OR

Authors and Affiliations

  1. Department of Paediatrics and Child Health, Flinders Medical Centre, The Flinders University of South Australia, Bedford Park, 5042, Adelaide, SA, Australia

    Brett G. Jeffrey

  2. Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 12420 Parklawn Dr., Rm. 1-14, 20852, Rockville, Maryland

    Drake C. Mitchell, Joseph R. Hibbeln & Norman Salem Jr.

  3. Child Nutrition Research Centre, Child Health Research Institute, 5000, Adelaide, SA, Australia

    Robert A. Gibson

  4. Unit of Laboratory Animal Science, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 20852, Rockville, Maryland

    A. Lee Chedester

Authors
  1. Brett G. Jeffrey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Drake C. Mitchell
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joseph R. Hibbeln
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert A. Gibson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Lee Chedester
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Norman Salem Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Norman Salem Jr..

Additional information

This study was conducted at the Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852.

About this article

Cite this article

Jeffrey, B.G., Mitchell, D.C., Hibbeln, J.R. et al. Visual acuity and retinal function in infant monkeys fed long-chain PUFA. Lipids 37, 839–848 (2002). https://doi.org/10.1007/s11745-002-0969-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-002-0969-0

Keywords

Search

Navigation