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Action Spectrum for Melatonin Suppression: Evidence for a Novel Circadian Photoreceptor in the Human Eye

  • George C. Brainard
  • John P. Hanifin

Abstract

Light is a potent regulator of systemic physiology. Specifically, environmental light is the primary stimulus for regulating circadian rhythms, seasonal cycles, and neuroendocrine responses in many mammalian species including humans (1,2,3,4). Shortly after the regulatory capacity of light was demonstrated in humans, light was tested as a therapeutic intervention for treating winter depression or Seasonal Affective Disorder (5,6,7). Since then, twenty years of clinical studies have confirmed that light therapy is effective for treating winter depression (8,9,10). In addition, light therapy has been studied as a treatment for selected circadian sleep disorders, nonseasonal depression, menstrual disturbances, eating disorders as well as re-entraining circadian physiology relative to the challenges of shift work or intercontinental air travel (11,12).

Keywords

Action Spectrum Light Therapy Melatonin Secretion Circadian Regulation Seasonal Affective Disorder 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Aschoff, J., ed. Handbook of Behavioral Neurobiology, Biological Rhythms. New York: Plenum Press, 1981.Google Scholar
  2. 2.
    Klein, DC, Moore, RY, Reppert, SM, eds. Suprachiasmatic Nucleus: The Mind’s Clock. Oxford: Oxford University Press, 1991.Google Scholar
  3. 3.
    Wehr, TA. The durations of human melatonin secretion and sleep respond to changes in daylength (photoperiod). J Clin Endocrinol Metab 1991;73:1276–80.PubMedCrossRefGoogle Scholar
  4. 4.
    Arendt, J. Melatonin and the pineal gland: influence on mammalian seasonal and circadian physiology. Rev Reprod 1998;3:13–22.PubMedCrossRefGoogle Scholar
  5. 5.
    Lewy, AJ, Wehr, TA, Goodwin, FK, Newsome, DA, Markey, SP. Light suppresses melatonin secretion in humans. Science 1980;210:1267–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Lewy, AJ, Kern, HE, Rosenthal, NE, Wehr, TA. Bright artificial light treatment of a manic-depressive patient with a seasonal mood cycle. Am J Psychiatry 1982;139:1496–8.PubMedGoogle Scholar
  7. 7.
    Rosenthal, NE, Sack, DA, Gillin, JC, Lewy, AJ, Goodwin, FK, Davenport, Y, Mueller, PS, Newsome, DA, Wehr, TA. Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy. Arch Gen Psychiatry 1984;41:72–80.PubMedCrossRefGoogle Scholar
  8. 8.
    Eastman, CI, Young, MA, Fogg, LF, Liu, L, Meaden, PM. Bright light treatment of winter depression: a placebo-controlled trial. Arch Gen Psychiatry 1998;55:883–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Terman, M, Terman, JS, Ross, DC. A controlled trial of timed bright light and negative air ionization for treatment of winter depression. Arch Gen Psychiatry 1998;55:875–82.PubMedCrossRefGoogle Scholar
  10. 10.
    Lewy, AJ, Bauer, VK, Cutler, NL, Sack, RL, Ahmed, S, Thomas, KH, Blood, ML, Jackson, JM. Morning vs evening light treatment of patients with winter depression. Arch Gen Psychiatry 1998;55:890–896.PubMedCrossRefGoogle Scholar
  11. 11.
    Wetterberg, L, ed. Light and Biological Rhythms in Man. Stockholm: Pergamon Press, 1993.Google Scholar
  12. 12.
    Lam, RW, ed. Seasonal Affective Disorder and Beyond: Light Treatment for SAD and Non-SAD Disorders. Washington, D.C.: American Psychiatric Press, 1998.Google Scholar
  13. 13.
    Moore, RY, Lenn, NJ. A retinohypothalamic projection in the rat. J Comp Neurol 1972;146:1–14.PubMedCrossRefGoogle Scholar
  14. 14.
    Card, JP. Pseudorabies virus and the functional architecture of the circadian timing system. J Biol Rhythms 2000;15:453–61.PubMedGoogle Scholar
  15. 15.
    Gaddy, JR, Rollag, MD, Brainard, GC. Pupil size regulation of threshold of light-induced melatonin suppression. J Clin Endocrinol Metab 1993;77:1398–1401.PubMedCrossRefGoogle Scholar
  16. 16.
    Brainard, GC, Rollag, MD, Hanifin, JP. Photic regulation of melatonin in humans: ocular and neural signal transduction. J Biol Rhythms 1997;12:537–46.PubMedCrossRefGoogle Scholar
  17. 17.
    Visser, EK, Beersma, DGM, Daan, S. Melatonin suppression by light in humans is maximal when the nasal part of the retina is illuminated. J Biol Rhythms 1999;14:116–21.PubMedCrossRefGoogle Scholar
  18. 18.
    Lasko, TA, Kripke, DF, Elliott, JA. Melatonin suppression by illumination of upper and lower visual fields. J Biol Rhythms 1999;14:122–5.PubMedCrossRefGoogle Scholar
  19. 19.
    Brainard, GC, Hanifin, JP, Rollag, MD, Greeson, J, Byrne, B, Glickman, G, Gerner, E, Sanford, B. Human melatonin regulation is not mediated by the three cone photopic visual system. J Clin Endocrinol Metab 2001;86:433–436.PubMedCrossRefGoogle Scholar
  20. 20.
    Brainard, GC, Hanifin, JP, Greeson, JM, Byrne, B, Glickman, G, Gerner, E, Rollag, MD. Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor. J Neurosci 2001;21:6405–6412.PubMedGoogle Scholar
  21. 21.
    Rodieck, RW. The First Steps in Seeing. Sunderland, Massachusetts: Sinauer Associates, Inc., 1998.Google Scholar
  22. 22.
    Pevet, P, Heth, G, Hiam, A, Nevo, E. Photoperiod perception in the blind mole rat (Spalax ehrenbergi, Nehring): involvement of the Harderian gland, atrophied eyes, and melatonin. J Exp Zool 1984;232:41–50.PubMedCrossRefGoogle Scholar
  23. 23.
    Webb, SM, Champney, TH, Lewinski, AK, Reiter, RJ. Photoreceptor damage and eye pigmentation: influence on the sensitivity of rat pineal N-acetyltransferase activity and melatonin levels to light at night. Neuroendocrinology 1985;40:205–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Goto, M, Ebihara, S. The influence of different light intensities on pineal melatonin content in the retinal degenerate C3H mouse and the normal CBA mouse. Neurosci Lett 1990;108:267–72.PubMedCrossRefGoogle Scholar
  25. 25.
    Foster, RG, Provencio, I, Hudson, D, Fiske, S, DeGrip, W, Menaker, M. Circadian photoreception in the retinally degenerate mouse (rd/rd). J Comp Physiol [A] 1991;169:39–50.Google Scholar
  26. 26.
    Provencio, I, Wong, S, Lederman, AB, Argamaso, SM, Foster, RG. Visual and circadian responses to light in aged retinally degenerate mice. Vision Res 1994;34:1799–1806.PubMedCrossRefGoogle Scholar
  27. 27.
    Yoshimura, T, Nishio, M, Goto, M, Ebihara, S. Differences in circadian photosensitivity between retinally degenerate CBA/J mice (rd/rd) and normal CBA/N mice (+/+). J Biol Rhythms 1994;9:51–60.PubMedCrossRefGoogle Scholar
  28. 28.
    García-Fernández, JM, Jiminez, AJ, Foster, RG. The persistence of cone photoreceptors within the dorsal retina of aged retinally degenerate mice (rd/rd): implications for circadian organization. Neurosci Lett 1995;187:33–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Provencio, I, Foster, RG. Circadian rhythms in mice can be regulated by photoreceptors with cone-like characteristics. Brain Res 1995;694:183–90.PubMedCrossRefGoogle Scholar
  30. 30.
    Yoshimura, T, Ebihara, S. Spectral sensitivity of photoreceptors mediating phase–shifts of circadian rhythms in retinally degenerate CBA/J (rd/rd) and normal CBA/N (+/+) mice. J Comp Physiol [A] 1996;178:797–802.Google Scholar
  31. 31.
    Lucas, RJ, Foster, RG. Neither functional rod photoreceptors nor rod or cone outer segments are required for the photic inhibition of pineal melatonin. Endocrinology 1999;140:1520–4.PubMedCrossRefGoogle Scholar
  32. 32.
    Freedman, MS, Lucas, RJ, Soni, B, von Schantz, M, Munoz, M, David-Gray, Z, Foster, RG. Regulation of mammalian circadian behavior by non–rod, non–cone, ocular photoreceptors. Science 1999;284:502–504.PubMedCrossRefGoogle Scholar
  33. 33.
    Sun, H, Gilbert, DJ, Copeland, NG, Jenkins, NA, Nathans, J. Peropsin, a novel visual pigment-like protein located in the apical microvilli of the retinal pigment epithelium. Proc Natl Acad Sci U S A 1997;94:9893–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Soni, BG, Foster, RG. A novel and ancient vertebrate opsin. FEBS Lett 1997;406:279–83.PubMedCrossRefGoogle Scholar
  35. 35.
    Provencio, I, Jiang, G, De Grip, WJ, Hayes, WP, Rollag, MD. Melanopsin: an opsin in melanophores, brain, and eye. Proc Natl Acad Sci U S A 1998;95:340–5.PubMedCrossRefGoogle Scholar
  36. 36.
    Oren, DA. Humoral phototransduction: blood is a messenger. The Neuroscientist 1996;2:207–10.CrossRefGoogle Scholar
  37. 37.
    Miyamoto, Y, Sancar, A. Vitamin B2-based blue-light photoreceptors in the retinohypothalamic tract as the photoactive pigments for setting the circadian clock in mammals. Proc Natl Acad Sci U S A 1998;95:6097–6102.PubMedCrossRefGoogle Scholar
  38. 38.
    Provencio, I, Rodriguez, IR, Jiang, G, Hayes, WP, Moreira, EF, Rollag, MD. A novel human opsin in the inner retina. J Neurosci 2000;20:600–5.PubMedGoogle Scholar
  39. 39.
    Ahmad, M, Cashmore, AR. HY4 gene of A. thaliana encodes a protein with characteristics of a blue-light photoreceptor. Nature 1993;366:162–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Stanewsky, R, Kaneko, M, Emery, P, et al. The cryb mutation identifies cryptochrome as a circadian photoreceptor in Drosophila. Cell 1998;95:681–92.PubMedCrossRefGoogle Scholar
  41. 41.
    Thresher, RJ, Vitaterna, MH, Miyamoto, Y, Kazantsev, A, Hsu, DS, Petit, C, Selby, CP, Dawut, L, Smithies, O, Takahashi, JS, Sancar, A, Role of mouse cryptochrome blue-light photoreceptor in circadian photoresponses. Science 1998;282:1490–1494.PubMedCrossRefGoogle Scholar
  42. 42.
    Griffin, EA, Staknis, D, Weitz, CJ. Light-independent role of Cry1 and Cry2 in the mammalian circadian clock. Science 1999;286:768–71.PubMedCrossRefGoogle Scholar
  43. 43.
    van der Horst, GTJ, Muijtjens, M, Kobayashi, K, Takano, R, Kanno, S, Takao, M, de Wit, J, Verkerk, A, Eker, APM, van Leenen, D, Buijs, R, Bootsma, D, Hoeijmakers, JHJ, Yasui, A. Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms. Nature 1999;398:627–630.PubMedCrossRefGoogle Scholar
  44. 44.
    von Schantz, M, Provencio, I, Foster, RG. Recent developments in circadian photoreception: more than meets the eye. Invest Ophthalmol Vis Sci 2000;41:1605–7.Google Scholar
  45. 45.
    Reppert, SM, Weaver, DR. Comparing clockworks: mouse versus fly. J Biol Rhythms 2000;15:357–64.PubMedCrossRefGoogle Scholar
  46. 46.
    Selby, CP, Thompson, C, Schmitz, TM, van Gelder, RN, Sancar, A. Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice. Proc Natl Acad Sci U S A 2000;97:14697–702.PubMedCrossRefGoogle Scholar
  47. 47.
    Berson, DM, Dunn, FA, Takao, M. Phototransduction by ganglion cells innervating the circadian pacemaker. San Diego, California, November 10–15: 31st Annual Meeting of the Society for Neuroscience, 2001. 27. abstract.Google Scholar
  48. 48.
    Czeisler, CA, Shanahan, TL, Klerman, EB, Martens, H, Brotman, DJ, Emens, JS, Klein, T, Rizzo, JF, III. Suppression of melatonin secretion in some blind patients by exposure to bright light. N Engl J Med 1995;332:6–11.PubMedCrossRefGoogle Scholar
  49. 49.
    Lockley, SW, Skene, DJ, Arendt, J, Tabandeh, H, Bird, AC, Defrace, R. Relationship between melatonin rhythms and visual loss in the blind. J Clin Endocrinol Metab 1997;82:3763–70.PubMedCrossRefGoogle Scholar
  50. 50.
    Skene, DJ, Lockley, SW, Thapan, K, Arendt, J. Effects of light on human circadian rhythms. Reprod Nutr Dev 1999;39:295–304.PubMedCrossRefGoogle Scholar
  51. 51.
    Ruberg, FL, Skene, DJ, Hanifin, JP, Rollag, MD, English, J, Arendt, J, Brainard, GC. Melatonin regulation in humans with color vision deficiencies. J Clin Endocrinol Metab 1996;81:2980–2985.PubMedCrossRefGoogle Scholar
  52. 52.
    Brainard, GC, Ruberg, FL, Hanifin, JP, Rollag, MD. The relationship of melatonin regulation and color vision in humans. In: Webb, SM, Puig-Domingo, M, M0ller, M, Pevét, P, eds. Pineal update: from molecular mechanisms to clinical implications. Westbury, New York: PJD Publications Ltd., 1997:339–48.Google Scholar
  53. 53.
    Grossweiner, LI. Photophysics. In: Smith, KC, ed. The science of photobiology. New York: Plenum Press, 1989:1–45.CrossRefGoogle Scholar
  54. 54.
    Coohill, TP. Action spectra again? Photochem Photobiol 1991;54:859–70.PubMedCrossRefGoogle Scholar
  55. 55.
    Lipson, ED. Action spectroscopy: methodology. In: Horspool, WM, Song, P-S, eds. Organic photochemistry and photobiology. New York: CRC Press, 1994:1257–66.Google Scholar
  56. 56.
    Brainard, GC, Lewy, AJ, Menaker, M, Miller, LS, Fredrickson, RH, Weleber, RG, Cassone, V, Hudson, D. Dose-response relationship between light irradiance and the suppression of melatonin in human volunteers. Brain Res 1988;454:212–218.PubMedCrossRefGoogle Scholar
  57. 57.
    Partridge, JC, De Grip, WJ. A new template for rhodopsin (vitamin Al based) visual pigments. Vision Res 1991;31:619–30.PubMedCrossRefGoogle Scholar
  58. 58.
    Stockman, A, Sharpe, LT. Cone spectral sensitivities and color matching. In: Gegenfurtner, KR, Sharpe, LT, eds. Color vision: from genes to perception. Cambridge, United Kingdom: Cambridge University Press, 1999:53–87.Google Scholar
  59. 59.
    Thapan, K, Arendt, J, Skene, DJ. An action spectrum for melatonin suppression: evidence for a novel non-rod, non-cone photoreceptor system in humans. J Physiol 2001;535:261–7.PubMedCrossRefGoogle Scholar
  60. 60.
    Brainard, GC. The healing light: interface of physics and biology. In: Lam, RW, ed. Seasonal Affective Disorder and beyond: light treatment for SAD and non-SAD conditions. Washington, D.C.: American Psychiatric Press, Inc., 1998:1–44.Google Scholar
  61. 61.
    Czeisler, CA, Allan, JS, Strogatz, SH, Ronda, JM, Sanchez, R, Rios, CD, Freitag, WO, Richardson, GS, Kronauer, RE. Bright light resets the human circadian pacemaker independent of the timing of the sleep-wake cycle. Science 1986;233:667–671.PubMedCrossRefGoogle Scholar
  62. 62.
    Nelson, DE, Takahashi, JS. Comparison of visual sensitivity for suppression of pineal melatonin and circadian phase-shifting in the golden hamster. Brain Res 1991;554:272–7.PubMedCrossRefGoogle Scholar
  63. 63.
    Zeitzer, JM, Dijk, D-J, Kronauer, RE, Brown, EN, Czeisler, CA. Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression. J Physiol 2000;526:695–702.PubMedCrossRefGoogle Scholar
  64. 64.
    Rea, MS, ed. Lighting Handbook: Reference & Application. New York: Illuminating Engineering Society of North America, 2000.Google Scholar
  65. 65.
    Society for Research on Biological Rhythms. Special Issue: Task force report on light treatment for sleep disorder. J Biol Rhythms 1995;10:99–176.CrossRefGoogle Scholar
  66. 66.
    Lam, RW, Tarn, EM, Gorman, CP, Blashko, C, Bowen, RC, Morehouse, RL, Hasey, GM. Light treatment. In: Lam, RW, Levitt, AJ, eds. Canadian consensus guidelines for the treatment of Seasonal Affective Disorder. Vancouver, British Columbia: Clinical and Academic Publishing, 1999:64–88.Google Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • George C. Brainard
    • 1
  • John P. Hanifin
    • 1
  1. 1.Department of Neurology, Jefferson Medical CollegeThomas Jefferson UniversityPhiladelphia

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