Illumination of different areas of the human retina elicits differences in acute light-induced suppression of melatonin. The aim of this study was to compare changes in plasma melatonin levels when light exposures of equal illuminance and equal photon dose were administered to superior, inferior, and full retinal fields. Nine healthy subjects participated in the study. Plexiglass eye shields were modified to permit selective exposure of the superior and inferior halves of the retinas of each subject. The Humphrey Visual Field Analyzer was used both to confirm intact full visual fields and to quantify exposure of upper and lower visual fields. On study nights, eyes were dilated, and subjects were exposed to patternless white light for 90 min between 0200 and 0330 under five conditions: (1) full retinal exposure at 200 lux, (2) full retinal exposure at 100 lux, (3) inferior retinal exposure at 200 lux, (4) superior retinal exposure at 200 lux, and (5) a dark-exposed control. Plasma melatonin levels were determined by radioimmunoassay. ANOVA demonstrated a significant effect of exposure condition (F = 5.91, p < 0.005). Post hoc Fisher PLSD tests showed significant (p [#003C] 0.05) melatonin suppression of both full retinal exposures as well as the inferior retinal exposure; however, superior retinal exposure was significantly less effective in suppressing melatonin. Furthermore, suppression with superior retinal exposure was not significantly different from that of the dark control condition. The results indicate that the inferior retina contributes more to the light-induced suppression of melatonin than the superior retina at the photon dosages tested in this study. Findings suggest a greater sensitivity or denser distribution of photoreceptors in the inferior retina are involved in light detection for the retinohypothalamic tract of humans.
References
1.
Adler JS, Kripke DF, Loving RT, and Berga SL (1992) Peripheral vision suppression of melatonin. J Pineal Res12:49-52.
2.
Aggelopoulos NC and Meissl H (2000) Responses of neurons of the rat suprachiasmatic nucleus to retinal illumination under photopic and scotopic conditions. J Physiol (Lond)523:211-222.
3.
Arendt J (1998) Melatonin and the pineal gland: Influence on mammalian seasonal and circadian physiology. Rev Reprod3:13-22.
4.
Berson DM, Dunn FA, and Takao M (2002) Phototransduction by retinal ganglion cells that set the circadian clock. Science295:1070-1073.
5.
Blackshaw S and Snyder SH (1999) Encephalopsin: a novel mammalian extraretinal opsin discretely localized in the brain. J Neurosci19:3681-3690.
6.
Brainard GC, Rollag MD, and Hanifin JP (1997) Photic regulation of melatonin in humans: Ocular and neural signal transduction. J Biol Rhythms12:537-546.
7.
Brainard GC, Hanifin JP, Greeson JM, Byrne B, Glickman G, Gerner E, and Rollag MD (2001a) Action spectrum for melatonin regulation in humans: Evidence for a novel circadian photoreceptor. J Neurosci21:6405-6412.
8.
Brainard GC, Hanifin JP, Rollag MD, Greeson J, Byrne B, Glickman G, Gerner E, and Sanford B (2001b) Human melatonin regulation is not mediated by the three cone photopic visual system. J Clin Endocrinol Metab86:433-436.
9.
Card JP (1994) Visual projections to the rodent hypothalamus. In Advances in Pineal Research: 8, M Møller and P Pévet, eds, pp 41-50, John Libby, London.
10.
Cooper HM, Tessonneaud A, Caldani A, Locatelli A, Richard S, and Viguier-Martinez MC (1993) Morphology and distribution of retinal ganglion cells (RGC) projecting to the suprachiasmatic nucleus in sheep [abstract]. Soc Neurosci Abstr19:1704.
11.
Curcio CA, Allen AA, Sloan KR, Lerea CL, Hurley JB, Klock IB, and Milam AH (1991) Distribution and morphology of human cone photoreceptors stained with anti-blue opsin. J Comp Neuro312:610-624.
12.
Czeisler CA, Shanahan TL, Klerman EB, Martens H, Brotman DJ, Emens JS, Klein T, and Rizzo JF, III (1995) Suppression of melatonin secretion in some blind patients by exposure to bright light. N Engl J Med332:6-11.
13.
Dkhissi-Benyahya O, Szel A, Degrip WJ, and Cooper HM (2001) Short and mid-wavelength cone distribution in a nocturnal Strepsirrhine primate (Microcebus murinus). J Comp Neurol438:490-504.
14.
Foster RG, Argamaso S, Coleman S, Colwell CS, Lederman A, and Provencio I (1993) Photoreceptors regulating circadian behavior: A mouse model. J Biol Rhythms8:S17-S23.
15.
Freedman MS, Lucas RJ, Soni B, von Schantz M, Munoz M, David-Gray Z, and Foster RG (1999) Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. Science284:502-504.
16.
Gaddy JR, Edelson M, Stewart K, Brainard GC, and Rollag MD (1992) Possible retinal spatial summation in melatonin suppression. In Biologic Effects of Light, MF Holick and AM Kligman, eds, pp 196-204, Walter de Gruyter, New York.
17.
Gaddy, JR, Rollag MD, and Brainard GC (1993) Pupil size regulation of threshold of light-induced melatonin suppression. J Clin Endocrinol Metab77:1398-1401.
18.
Gooley JJ, Lu J, Chou TC, Scammell TE, and Saper CB (2001) Melanopsin in cell of origin of the retinohypothalamic tract. Nature Neurosci4:1165.
19.
Hannibal J, Hindersson P, Knudsen SM, Georg B, and Fahrenkrug J (2002) The photopigment melanopsin is exclusively present in pituitary adenylate cyclase-activating polypeptide containing retinal ganglion cells of the retinohypothalamic tract. J Neurosci22(RC191):1-7.
20.
Hattar S, Liao H-W, Takao M, Berson DM, and Yau K-W (2002) Melanopsin-containing retinal ganglion cells: Architecture, projections, and intrinsic photosensitivity. Science295:1065-1070.
21.
Klein DC, Moore RY, and Reppert SM, editors (1991) Suprachiasmatic Nucleus: The Mind’s Clock, Oxford University Press, Oxford.
22.
Klein DC and Weller JL (1972) Rapid light-induced decrease in pineal serotonin N-acetyltransferase activity. Science177:532-533.
23.
Lam RW, editor (1998) Seasonal Affective Disorder and Beyond: Light Treatment for SAD and Non-SAD Disorders, American Psychiatric Press, Washington, DC.
24.
Lasko TA, Kripke DF, and Elliott JA (1999) Melatonin suppression by illumination of upper and lower visual fields. J Biol Rhythms14:122-125.
25.
Lucas RJ, Freedman MS, Munoz M, Garcia-Fernandez JM, and Foster RG (1999) Regulation of the mammalian pineal by non-rod, non-cone, ocular photoreceptors. Science284:505-507.
26.
Lucas RJ, Douglas RH, and Foster RG (2001) Characterization of an ocular photopigment capable of driving pupillary constriction in mice. Nature Neurosci4:621-626.
27.
Lupi D, Cooper HM, Froehlich A, Standford L, McCall MA, and Foster RG (1999) Transgenic ablation of rod photoreceptors alters the circadian phenotype of mice. Neuroscience89:363-374.
28.
Magnin M, Cooper HM, and Mick G (1989) Retinohypothalamic pathway: A breach in the law of Newton-Muller-Gudden? Brain Res488:390-397.
29.
Miyamoto Y and Sancar A (1998) 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 A95:6097-6102.
30.
Moore RY, Speh JC, and Card JP (1995) The retinohypothalamic tract originates from a distinct subset of retinal ganglion cells. J Comp Neurol352:351-366.
31.
Nelson DE and Takahashi JS (1991) Sensitivity and integration in a visual pathway for circadian entrainment in the hamster (Mesocricetus auratus). J Physiol439:115-145.
32.
Nelson DE and Takahashi JS (1999) Integration and saturation within the circadian photic entrainment pathway of hamsters. Am J Physiol277(5 Pt 2):R1351-1361.
33.
Provencio I and Foster RG (1995) Circadian rhythms in mice can be regulated by photoreceptors with cone-like characteristics. Brain Res694:183-190.
34.
Provencio I, Jiang G, De Grip WJ, Hayes WP, and Rollag MD (1998) Melanopsin: An opsin in melanophores, brain, and eye. Proc Natl Acad Sci U S A95:340-345.
35.
Provencio I, Rodriguez IR, Jiang G, Hayes WP, Moreira EF, and Rollag MD (2000) A novel human opsin in the inner retina. J Neurosci20:600-605.
36.
Provencio I, Rollag MD, and Castrucci AM (2002) Photoreceptive net in the mammalian retina. Nature415:493.
37.
Rollag MD and Niswender GD (1976) Radioimmunoassay of serumconcentrations of melatonin in sheep exposed to different lighting regimens. Endocrinology98:482-489.
38.
Ruberg FL, Skene DJ, Hanifin JP, Rollag MD, English J, Arendt J, and Brainard GC(1996) Melatonin regulation in humans with color vision deficiencies. J Clin Endocrinol Metab81:2980-2985.
39.
Schwartz WJ, Busis NA, and Hedley-Whyte ET (1986) A discrete lesion of ventral hypothalamus and optic chiasm that disturbed the daily temperature rhythm. J Neurol233:1-4.
40.
Soni BG and Foster RG (1997) A novel and ancient vertebrate opsin. FEBS Letters406:279-283.
41.
Szel A, Rohlich P, Caffe AR, and van Veen T (1996) Distribution of cone photoreceptors in the mammalian retina. Microsc Res Technique35:445-462.
42.
Szel A, Lukats A, Fekete T, Szepessy Z, and Rohlich P (2000) Photoreceptor distribution in the retinas of subprimate mammals. J Opt Soc Am [A]17:568-579.
43.
Takahashi JS, DeCoursey PJ, Bauman L, and Menaker M (1984) Spectral sensitivity of a novel photoreceptive system mediating entrainment of mammalian circadian rhythms. Nature308:186-188.
44.
Thapan K, Arendt J, and Skene DJ (2001) An action spectrum for melatonin suppression: Evidence for a novel non-rod, non-cone photoreceptor system in humans. J Physiol535:261-267.
45.
Visser EK, Beersma DGM, and Daan S (1999) Melatonin suppression by light in humans is maximal when the nasal part of the retina is illuminated. J Biol Rhythms14:116-121.
46.
Wang JY, Hanifin JP, Rollag MD, and Brainard GC (1997) Ocular regulation of the human pineal gland: The significance of total retinal exposure for melatonin suppression. In Biologic Effects of Light 1998, M Holick and EG Jung, eds, pp 367-374, Kluwer Academic, Boston.
