Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-25T05:20:42.141Z Has data issue: false hasContentIssue false
  • English
  • Français

Role of melatonin in the eye and ocular dysfunctions

Published online by Cambridge University Press:  30 January 2007

PER O. LUNDMARK ,
SEITHIKURIPPU R. PANDI-PERUMAL ,
VENKATARAMANUJAN SRINIVASAN  and
DANIEL P. CARDINALI
PER O. LUNDMARK
Affiliation:
Department of Optometry and Vision Sciences, Buskerud University College, Kongsberg, Norway
SEITHIKURIPPU R. PANDI-PERUMAL
Affiliation:
Comprehensive Center for Sleep Medicine, Department of Pulmonary, Critical Care and Sleep Medicine, Mount Sinai School of Medicine, New York, New York
VENKATARAMANUJAN SRINIVASAN
Affiliation:
Department of Physiology, School of Medical Sciences, University Sains Malaysia, Kubang kerian, Kelantan, Malaysia
DANIEL P. CARDINALI
Affiliation:
Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
Get access Rights & Permissions [Opens in a new window]

Abstract

Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi, and animals. Several studies have indicated that melatonin synthesis occurs in the retina of most vertebrates, including mammals. The retinal biosynthesis of melatonin and the mechanisms involved in the regulation of this process have been extensively studied. Circadian clocks located in the photoreceptors and retinal neurons regulate melatonin synthesis in the eye. Photoreceptors, dopaminergic amacrine neurons, and horizontal cells of the retina, corneal epithelium, stroma endothelium, and the sclera all have melatonin receptors, indicating a widespread ocular function for melatonin. In addition, melatonin is an effective antioxidant which scavenges free radicals and up-regulates several antioxidant enzymes. It also has a strong antiapoptotic signaling function, an effect that it exerts even during ischemia. Melatonin cytoprotective properties may have practical implications in the treatment of ocular diseases, like glaucoma and age-related macular degeneration.

Keywords

MelatoninRetinal phototransductionIntraocular pressureCorneal epitheliumAntioxidants
Type
Research Article
Information
Visual Neuroscience , Volume 23 , Issue 6 , November 2006 , pp. 853 - 862
Copyright
© 2006 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Adachi, A., Suzuki, Y., Nogi, T., & Ebihara, S. (1999). The relationship between ocular melatonin and dopamine rhythms in the pigeon: Effects of melatonin inhibition on dopamine release. Brain Research 815, 435–440.Google Scholar
Age-Related Eye Disease Study Research Group. (2001). A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Archives of Ophthalmology 119, 1417–1436.Google Scholar
Alonso-Gomez, A.L. & Iuvone, P.M. (1995). Melatonin biosynthesis in cultured chick retinal photoreceptor cells: Calcium and cyclic AMP protect serotonin N-acetyltransferase from inactivation in cycloheximide-treated cells. Journal of Neurochemistry 65, 1054–1060.Google Scholar
Arendt, J. & Skene, D.J. (2005). Melatonin as a chronobiotic. Sleep Medicine Reviews 9, 25–39.Google Scholar
Avery, R.L., Fekrat, S., Hawkins, B.S., & Bressler, N.M. (1996). Natural history of subfoveal subretinal hemorrhage in age-related macular degeneration. Retina 16, 183–189.Google Scholar
Axelrod, J. (1974). The pineal gland: A neurochemical transducer. Science 184, 1341–1348.Google Scholar
Bailey, M.J., Chong, N.W., Xiong, J., & Cassone, V.M. (2002). Chickens' Cry2: Molecular analysis of an avian cryptochrome in retinal and pineal photoreceptors. Federation of European Biochemical Societies Letters 513, 169–174.Google Scholar
Bayarri, M.J., Rol de Lama, M.A., Madrid, J.A., & Sanchez-Vazquez, F.J. (2003). Both pineal and lateral eyes are needed to sustain daily circulating melatonin rhythms in sea bass. Brain Research 969, 175–182.Google Scholar
Benitez-King, G., Rios, A., Martinez, A., & Anton-Tay, F. (1996). In vitro inhibition of Ca2+/calmodulin-dependent kinase II activity by melatonin. Biochimica Biophysica Acta 1290, 191–196.Google Scholar
Bernard, M., Donohue, S.J., & Klein, D.C. (1995). Human hydroxyindole-O-methyltransferase in pineal gland, retina and Y79 retinoblastoma cells. Brain Research 696, 37–48.Google Scholar
Bernard, M., Guerlotte, J., Greve, P., Grechez-Cassiau, A., Iuvone, M.P., Zatz, M., Chong, N.W., Klein, D.C., & Voisin, P. (1999). Melatonin synthesis pathway: Circadian regulation of the genes encoding the key enzymes in the chicken pineal gland and retina. Reproduction, Nutrition, Development 39, 325–334.Google Scholar
Bernard, M., Klein, D.C., & Zatz, M. (1997). Chick pineal clock regulates serotonin N-acetyltransferase mRNA rhythm in culture. Proceedings of the National Academy of Science USA 94, 304–309.Google Scholar
Berson, D.M. (2003). Strange vision: Ganglion cells as circadian photoreceptors. Trends Neuroscience 26, 314–320.Google Scholar
Berson, D.M., Dunn, F.A., & Takao, M. (2002). Phototransduction by retinal ganglion cells that set the circadian clock. Science 295, 1070–1073.Google Scholar
Besharse, J.C. & Dunis, D.A. (1983). Methoxyindoles and photoreceptor metabolism: Activation of rod shedding. Science 219, 1341–1343.Google Scholar
Brainard, G.C., Hanifin, J.P., Greeson, J.M., Byrne, B., Glickman, G., Gerner, E., & Rollag, M.D. (2001a). Action spectrum for melatonin regulation in humans: Evidence for a novel circadian photoreceptor. Journal of Neuroscience 21, 6405–6412.Google Scholar
Brainard, G.C., Hanifin, J.P., Rollag, M.D., Greeson, J., Byrne, B., Glickman, G., Gerner, E., & Sanford, B. (2001b). Human melatonin regulation is not mediated by the three cone photopic visual system. Journal of Clinical Endocrinology and Metabolism 86, 433–436.Google Scholar
Brun, J., Claustrat, B., Saddier, P., & Chazot, G. (1995). Nocturnal melatonin excretion is decreased in patients with migraine without aura attacks associated with menses. Cephalalgia 15, 136–139.Google Scholar
Brydon, L., Petit, L., de Coppet, P., Barrett, P., Morgan, P.J., Strosberg, A.D., & Jockers, R. (1999a). Polymorphism and signalling of melatonin receptors. Reproduction, Nutrition and Development 39, 315–324.Google Scholar
Brydon, L., Roka, F., Petit, L., de Coppet, P., Tissot, M., Barrett, P., Morgan, P.J., Nanoff, C., Strosberg, A.D., & Jockers, R. (1999b). Dual signaling of human Mel1a melatonin receptors via Gi2, Gi3, and Gq/11 proteins. Molecular Endocrinology 13, 2025–2038.Google Scholar
Bunin, A.I., Filina, A.A., & Erichev, V.P. (1992). A glutathione deficiency in open-angle glaucoma and the approaches to its correction. Vestnik oftalmologii 108, 13–15.Google Scholar
Cagnacci, A., Cannoletta, M., Renzi, A., Baldassari, F., Arangino, S., & Volpe, A. (2005). Prolonged melatonin administration decreases nocturnal blood pressure in women. American Journal of Hypertension 18, 1614–1618.Google Scholar
Cahill, G.M. & Besharse, J.C. (1993). Circadian clock functions localized in xenopus retinal photoreceptors. Neuron 10, 573–577.Google Scholar
Cai, J., Nelson, K.C., Wu, M., Sternberg, P., Jr., & Jones, D.P. (2000). Oxidative damage and protection of the RPE. Progress in Retina and Eye Research 19, 205–221.Google Scholar
Cajochen, C., Krauchi, K., & Wirz-Justice, A. (2003). Role of melatonin in the regulation of human circadian rhythms and sleep. Journal of Neuroendocrinology 15, 432–437.Google Scholar
Cardinali, D.P. & Freire, F. (1975). Melatonin effects on brain. Interaction with microtubule protein, inhibition of fast axoplasmic flow and induction of crystaloid and tubular formations in the hypothalamus. Molecular and Cellular Endocrinology 2, 317–330.Google Scholar
Cardinali, D.P. & Rosner, J.M. (1971a). Metabolism of serotonin by the rat retina “in vitro”. Journal of Neurochemistry 18, 1769–1770.Google Scholar
Cardinali, D.P. & Rosner, J.M. (1971b). Retinal localization of the hydroxyindole-O-methyl transferase (HIOMT) in the rat. Endocrinology 89, 301–303.Google Scholar
Carrillo-Vico, A., Garcia-Perganeda, A., Naji, L., Calvo, J.R., Romero, M.P., & Guerrero, J.M. (2003). Expression of membrane and nuclear melatonin receptor mRNA and protein in the mouse immune system. Cellular and Molecular Life Sciences 60, 2272–2278.Google Scholar
Chaurasia, S.S., Rollag, M.D., Jiang, G., Hayes, W.P., Haque, R., Natesan, A., Zatz, M., Tosini, G., Liu, C., Korf, H.W., Iuvone, P.M., & Provencio, I. (2005). Molecular cloning, localization and circadian expression of chicken melanopsin (Opn4): Differential regulation of expression in pineal and retinal cell types. Journal of Neurochemistry 92, 158–170.Google Scholar
Chazot, G., Claustrat, B., Brun, J., Jordan, D., Sassolas, G., & Schott, B. (1984). A chronobiological study of melatonin, cortisol growth hormone and prolactin secretion in cluster headache. Cephalalgia 4, 213–220.Google Scholar
Chen, G., Huo, Y., Tan, D.X., Liang, Z., Zhang, W., & Zhang, Y. (2003). Melatonin in Chinese medicinal herbs. Life Sciences 73, 19–26.Google Scholar
Chen, W. & Baler, R. (2000). The rat arylalkylamine N-acetyltransferase E-box: Differential use in a master vs. a slave oscillator. Brain Research. Molecular Brain Research 81, 43–50.Google Scholar
Chong, N.W., Cassone, V.M., Bernard, M., Klein, D.C., & Iuvone, P.M. (1998). Circadian expression of tryptophan hydroxylase mRNA in the chicken retina. Brain Research Molecular Brain Research 61, 243–250.Google Scholar
Chronicle, E.P. & Mulleners, W.M. (1996). Visual system dysfunction in migraine: A review of clinical and psychophysical findings. Cephalalgia 16, 525–535.Google Scholar
Claustrat, B., Brun, J., & Chazot, G. (2005). The basic physiology and pathophysiology of melatonin. Sleep Medicine Reviews 9, 11–24.Google Scholar
Claustrat, B., Brun, J., Chiquet, C., Chazot, G., & Borson-Chazot, F. (2004). Melatonin secretion is supersensitive to light in migraine. Cephalalgia 24, 128–133.Google Scholar
Claustrat, B., Loisy, C., Brun, J., Beorchia, S., Arnaud, J.L., & Chazot, G. (1989). Nocturnal plasma melatonin levels in migraine: A preliminary report. Headache 29, 242–245.Google Scholar
Coon, S.L., Del Olmo, E., Young, W.S., III, & Klein, D.C. (2002). Melatonin synthesis enzymes in Macaca mulatta: Focus on arylalkylamine N-acetyltransferase (EC 2.3.1.87). Journal of Clinical Endocrinology and Metabolism 87, 4699–4706.Google Scholar
Cruickshanks, K.J., Klein, R., Klein, B.E., & Nondahl, D.M. (2001). Sunlight and the 5-year incidence of early age-related maculopathy: The beaver dam eye study. Archives of Ophthalmology 119, 246–250.Google Scholar
Cuzzocrea, S. & Reiter, R.J. (2002). Pharmacological actions of melatonin in acute and chronic inflammation. Current Topics in Medicinal Chemistry 2, 153–165.Google Scholar
Deshmukh, V.D. (2006). Retino-hypothalamic-pineal hypothesis in the pathophysiology of primary headaches. Medical Hypotheses 66, 1146–1151.Google Scholar
Dodick, D.W., Eross, E.J., Parish, J.M., & Silber, M. (2003). Clinical, anatomical, and physiologic relationship between sleep and headache. Headache 43, 282–292.Google Scholar
Doughty, M.J. (1990). Morphometric analysis of the surface cells of rabbit corneal epithelium by scanning electron microscopy. The American Journal of Anatomy 189, 316–328.Google Scholar
Dreyer, E.B., Pan, Z.H., Storm, S., & Lipton, S.A. (1994). Greater sensitivity of larger retinal ganglion cells to NMDA-mediated cell death. Neuroreport 5, 629–631.Google Scholar
Dreyer, E.B., Zurakowski, D., Schumer, R.A., Podos, S.M., & Lipton, S.A. (1996). Elevated glutamate levels in the vitreous body of humans and monkeys with glaucoma. Archives of Ophthalmology 114, 299–305.Google Scholar
Dubocovich, M.L. (1984). N-Acetyltryptamine antagonizes the melatonin-induced inhibition of [3H]dopamine release from retina. The European Journal of Pharmacology 105, 193–194.Google Scholar
Dubocovich, M.L., Hudson, R.L., Sumaya, I.C., Masana, M.I., & Manna, E. (2005). Effect of MT1 melatonin receptor deletion on melatonin-mediated phase shift of circadian rhythms in the C57BL/6 mouse. Journal of Pineal Research 39, 113–120.Google Scholar
Dubocovich, M.L. & Markowska, M. (2005). Functional MT1 and MT2 melatonin receptors in mammals. Endocrine 27, 101–110.Google Scholar
Dubocovich, M.L., Yun, K., Al-Ghoul, W.M., Benloucif, S., & Masana, M.I. (1998). Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms. The Federation of European Biochemical Journal 12, 1211–1220.Google Scholar
Esquifino, A.I., Pandi-Perumal, S.R., & Cardinali, D.P. (2004). Circadian organization of the immune response: A role for melatonin. Clinical and Applied Immunology Reviews 4, 423–433.Google Scholar
Foster, R.G. & Hankins, M.W. (2002). Non-rod, non-cone photoreception in the vertebrates. Progress in Retinal and Eye Research 21, 507–527.Google Scholar
Fujieda, H., Hamadanizadeh, S.A., Wankiewicz, E., Pang, S.F., & Brown, G.M. (1999). Expression of mt1 melatonin receptor in rat retina: Evidence for multiple cell targets for melatonin. Neuroscience 93, 793–799.Google Scholar
Fujieda, H., Scher, J., Hamadanizadeh, S.A., Wankiewicz, E., Pang, S.F., & Brown, G.M. (2000). Dopaminergic and GABAergic amacrine cells are direct targets of melatonin: Immunocytochemical study of mt1 melatonin receptor in guinea pig retina. Visual Neuroscience 17, 63–70.Google Scholar
Fukuhara, C. (2004). Effect of dark exposure in the middle of the day on Period1, Period2, and arylalkylamine N-acetyltransferase mRNA levels in the rat suprachiasmatic nucleus and pineal gland. Brain Research. Molecular Brain Research 130, 109–114.Google Scholar
Fukuhara, C., Dirden, J.C., & Tosini, G. (2001). Photic regulation of melatonin in rat retina and the role of proteasomal proteolysis. Neuroreport 12, 3833–3837.Google Scholar
Fukuhara, C., Dirden, J.C., & Tosini, G. (2002). Regulation of period 1 expression in cultured rat pineal. Neurosignals 11, 103–114.Google Scholar
Fukuhara, C., Liu, C., Ivanova, T.N., Chan, G.C., Storm, D.R., Iuvone, P.M., & Tosini, G. (2004). Gating of the cAMP signaling cascade and melatonin synthesis by the circadian clock in mammalian retina. Journal of Neuroscience 24, 1803–1811.Google Scholar
Gan, J., Alonso-Gomez, A.L., Avendano, G., Johnson, B., & Iuvone, P.M. (1995). Melatonin biosynthesis in photoreceptor-enriched chick retinal cell cultures: Role of cyclic AMP in the K+-evoked, Ca2+-dependent induction of serotonin N-acetyltransferase activity. Neurochemistry International 27, 147–155.Google Scholar
Godson, C. & Reppert, S.M. (1997). The Mel1a melatonin receptor is coupled to parallel signal transduction pathways. Endocrinology 138, 397–404.Google Scholar
Gooley, J.J., Lu, J., Chou, T.C., Scammell, T.E., & Saper, C.B. (2001). Melanopsin in cells of origin of the retinohypothalamic tract. Nature Neuroscience 4, 1165.Google Scholar
Green, C.B., Cahill, G.M., & Besharse, J.C. (1995). Regulation of tryptophan hydroxylase expression by a retinal circadian oscillator in vitro. Brain Research 677, 283–290.Google Scholar
Green, W.R. & Key, S.N., III. (1977). Senile macular degeneration: A histopathologic study. Transactions of the American Ophthalmological Society 75, 180–254.Google Scholar
Green, W.R., McDonnell, P.J., & Yeo, J.H. (2005). Pathologic features of senile macular degeneration. 1985. Retina 25, 615–627.Google Scholar
Greve, P., Alonso-Gomez, A., Bernard, M., Ma, M., Haque, R., Klein, D.C., & Iuvone, P.M. (1999). Serotonin N-acetyltransferase mRNA levels in photoreceptor-enriched chicken retinal cell cultures: Elevation by cyclic AMP. Journal of Neurochemistry 73, 1894–1900.Google Scholar
Guerrero, J.M. & Reiter, R.J. (2002). Melatonin-immune system relationships. Current Topics in Medicinal Chemistry 2, 167–179.Google Scholar
Hammond, B.R., Jr., Wooten, B.R., & Snodderly, D.M. (1996). Cigarette smoking and retinal carotenoids: Implications for age-related macular degeneration. Vision Research 36, 3003–3009.Google Scholar
Hampson, E.C., Vaney, D.I., & Weiler, R. (1992). Dopaminergic modulation of gap junction permeability between amacrine cells in mammalian retina. Journal of Neuroscience 12, 4911–4922.Google Scholar
Haque, R., Chaurasia, S.S., Wessel, J.H., III, & Iuvone, P.M. (2002). Dual regulation of cryptochrome 1 mRNA expression in chicken retina by light and circadian oscillators. Neuroreport 13, 2247–2251.Google Scholar
Hardeland, R., Behrmann, G., Fuhrberg, B., Poeggeler, B., Burkhardt, S., Uria, H., & Obst, B. (1996). Evolutionary aspects of indoleamines as radical scavengers. Presence and photocatalytic turnover of indoleamines in a unicell, Gonyaulax polyedra. Advances in Expimental Medicine and Biology 398, 279–284.Google Scholar
Hardeland, R., Coto-Montes, A., & Poeggeler, B. (2003). Circadian rhythms, oxidative stress, and antioxidative defense mechanisms. Chronobiology International 20, 921–962.Google Scholar
Hardeland, R. & Pandi-Perumal, SR. (2005). Melatonin, a potent agent in antioxidative defense: Actions as a natural food constituent, gastrointestinal factor, drug and prodrug. Nutrition and Metabolism (Lond) 2, 22.Google Scholar
Hardeland, R., Pandi-Perumal, S.R., & Cardinali, D.P. (2006). Melatonin. The International Journal of Biochemistry and Cell Biology 38, 313–316.Google Scholar
Hattar, S., Liao, H.W., Takao, M., Berson, D.M., & Yau, K.W. (2002). Melanopsin-containing retinal ganglion cells: Architecture, projections, and intrinsic photosensitivity. Science 295, 1065–1070.Google Scholar
Hay, K.M., Mortimer, M.J., Barker, D.C., Debney, L.M., & Good, P.A. (1994). 1044 women with migraine: The effect of environmental stimuli. Headache 34, 166–168.Google Scholar
Hoffmann, M. & Schaeffel, F. (1996). Melatonin and deprivation myopia in chickens. Neurochemistry International 28, 95–107.Google Scholar
Hughes, R.J. & Badia, P. (1997). Sleep-promoting and hypothermic effects of daytime melatonin administration in humans. Sleep 20, 124–131.Google Scholar
Hunt, A.E., Al-Ghoul, W.M., Gillette, M.U., & Dubocovich, M.L. (2001). Activation of MT2 melatonin receptors in rat suprachiasmatic nucleus phase advances the circadian clock. American Journal of Physiology. Cell Physiology 280, C110–C118.Google Scholar
Iuvone, P.M., Brown, A.D., Haque, R., Weller, J., Zawilska, J.B., Chaurasia, S.S., Ma, M., & Klein, D.C. (2002). Retinal melatonin production: Role of proteasomal proteolysis in circadian and photic control of arylalkylamine N-acetyltransferase. Investigative Ophthalmology and Visual Science 43, 564–572.Google Scholar
Iuvone, P.M., Chong, N.W., Bernard, M., Brown, A.D., Thomas, K.B., & Klein, D.C. (1999). Melatonin biosynthesis in chicken retina. Regulation of tryptophan hydroxylase and arylalkylamine N-acetyltransferase. Advances of Experimental Medicine and Biology 460, 31–41.Google Scholar
Iuvone, P.M. & Gan, J. (1995). Functional interaction of melatonin receptors and D1 dopamine receptors in cultured chick retinal neurons. Journal of Neuroscience 15, 2179–2185.Google Scholar
Iuvone, P.M., Gan, J., & Avendano, G. (1991). K+-evoked depolarization stimulates cyclic AMP accumulation in photoreceptor-enriched retinal cell cultures: Role of calcium influx through dihydropyridine-sensitive calcium channels. Journal of Neurochemistry 57, 615–621.Google Scholar
Iuvone, P.M., Tosini, G., Pozdeyev, N., Haque, R., Klein, D.C., & Chaurasia, S.S. (2005). Circadian clocks, clock networks, arylalkylamine N-acetyltransferase, and melatonin in the retina. Progress in Retinal and Eye Research 24, 433–456.Google Scholar
Ivanova, T.N. & Iuvone, P.M. (2003a). Circadian rhythm and photic control of cAMP level in chick retinal cell cultures: A mechanism for coupling the circadian oscillator to the melatonin-synthesizing enzyme, arylalkylamine N-acetyltransferase, in photoreceptor cells. Brain Research 991, 96–103.Google Scholar
Ivanova, T.N. & Iuvone, P.M. (2003b). Melatonin synthesis in retina: Circadian regulation of arylalkylamine N-acetyltransferase activity in cultured photoreceptor cells of embryonic chicken retina. Brain Research 973, 56–63.Google Scholar
Jaliffa, C.O., Faillace, M.P., Lacoste, F.F., Llomovatte, D.W., Keller Sarmiento, M.I., & Rosenstein, R.E. (1999). Effect of GABA on melatonin content in golden hamster retina. Journal of Neurochemistry 72, 1999–2005.Google Scholar
Jaliffa, C.O., Lacoste, F.F., Llomovatte, D.W., Sarmiento, M.I., & Rosenstein, R.E. (2000). Dopamine decreases melatonin content in golden hamster retina. The Journal of Pharmacology and Experimental Therapeutics 293, 91–95.Google Scholar
Jaliffa, C.O., Saenz, D., Resnik, E., Keller Sarmiento, M.I., & Rosenstein, R.E. (2001). Circadian activity of the GABAergic system in the golden hamster retina. Brain Research 912, 195–202.Google Scholar
Karasek, M. (2004). Melatonin, human aging, and age-related diseases. Experimental Gerontology 39, 1723–1729.Google Scholar
Klein, B.E. & Klein, R. (1982). Cataracts and macular degeneration in older Americans. Archives of Ophthalmology 100, 571–573.Google Scholar
Knepper, P.A., Goossens, W., Hvizd, M., & Palmberg, P.F. (1996). Glycosaminoglycans of the human trabecular meshwork in primary open-angle glaucoma. Investigative Ophthalmology and Visual Science 37, 1360–1367.Google Scholar
Kvetnoy, I. (2002). Extrapineal melatonin in pathology: New perspectives for diagnosis, prognosis and treatment of illness. Neuro Endocrinology Letters 23, Suppl 1, 92–96.Google Scholar
Lerner, A.B. & Case, M.D. (1960). Melatonin. Federation Proceedings 19, 590–592.Google Scholar
Liang, F.Q., Aleman, T.S., Zaixin, Y., Cideciyan, A.V., Jacobson, S.G., & Bennett, J. (2001). Melatonin delays photoreceptor degeneration in the rds/rds mouse. Neuroreport 12, 1011–1014.Google Scholar
Liang, F.Q. & Godley, B.F. (2003). Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: A possible mechanism for RPE aging and age-related macular degeneration. Experimental Eye Research 76, 397–403.Google Scholar
Liang, F.Q., Green, L., Wang, C., Alssadi, R., & Godley, B.F. (2004). Melatonin protects human retinal pigment epithelial (RPE) cells against oxidative stress. Experimental Eye Research 78, 1069–1075.Google Scholar
Liu, C., Fukuhara, C., Wessel, J.H., III, Iuvone, P.M., & Tosini, G. (2004). Localization of Aa-nat mRNA in the rat retina by fluorescence in situ hybridization and laser capture microdissection. Cell Tissue Research 315, 197–201.Google Scholar
Liu, C., Weaver, D.R., Jin, X., Shearman, L.P., Pieschl, R.L., Gribkoff, V.K., & Reppert, S.M. (1997). Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron 19, 91–102.Google Scholar
Marchiafava, P.L. & Longoni, B. (1999). Melatonin as an antioxidant in retinal photoreceptors. Journal of Pineal Research 26, 184–189.Google Scholar
Martin, X.D., Malina, H.Z., Brennan, M.C., Hendrickson, P.H., & Lichter, P.R. (1992). The ciliary body–the third organ found to synthesize indoleamines in humans. European Journal of Ophthalmology 2, 67–72.Google Scholar
McArthur, A.J., Hunt, A.E., & Gillette, M.U. (1997). Melatonin action and signal transduction in the rat suprachiasmatic circadian clock: Activation of protein kinase C at dusk and dawn. Endocrinology 138, 627–634.Google Scholar
McGoogan, J.M. & Cassone, V.M. (1999). Circadian regulation of chick electroretinogram: Effects of pinealectomy and exogenous melatonin. American Journal of Physiology 277, R1418–R1427.Google Scholar
Meyer, P., Pache, M., Loeffler, K.U., Brydon, L., Jockers, R., Flammer, J., Wirz-Justice, A., & Savaskan, E. (2002). Melatonin MT-1-receptor immunoreactivity in the human eye. British Journal of Ophthalmology 86, 1053–1057.Google Scholar
Mhatre, M.C., van Jaarsveld, A.S., & Reiter, R.J. (1988). Melatonin in the lacrimal gland: First demonstration and experimental manipulation. Biochemistry and Biophysiology Research Communications 153, 1186–1192.Google Scholar
Moreno, M.C., Campanelli, J., Sande, P., Sanez, D.A., Keller Sarmiento, M.I., & Rosenstein, R.E. (2004). Retinal oxidative stress induced by high intraocular pressure. Free Radical Biology and Medicine 37, 803–812.Google Scholar
Namihira, M., Honma, S., Abe, H., Masubuchi, S., Ikeda, M., & Honmaca, K. (2001). Circadian pattern, light responsiveness and localization of rPer1 and rPer2 gene expression in the rat retina. Neuroreport 12, 471–475.Google Scholar
Natesan, A.K. & Cassone, V.M. (2002). Melatonin receptor mRNA localization and rhythmicity in the retina of the domestic chick, Gallus domesticus. Visual Neuroscience 19, 265–274.Google Scholar
Nguyen-Legros, J., Chanut, E., Versaux-Botteri, C., Simon, A., & Trouvin, J.H. (1996). Dopamine inhibits melatonin synthesis in photoreceptor cells through a D2-like receptor subtype in the rat retina: Biochemical and histochemical evidence. Journal of Neurochemistry 67, 2514–2520.Google Scholar
Nickells, R.W. (1996). Retinal ganglion cell death in glaucoma: The how, the why, and the maybe. Journal of Glaucoma 5, 345–356.Google Scholar
Niki, T., Hamada, T., Ohtomi, M., Sakamoto, K., Suzuki, S., Kako, K., Hosoya, Y., Horikawa, K., & Ishida, N. (1998). The localization of the site of arylalkylamine N-acetyltransferase circadian expression in the photoreceptor cells of mammalian retina. Biochemistry Biophysiology and Research Communications 248, 115–120.Google Scholar
Nosjean, O., Ferro, M., Coge, F., Beauverger, P., Henlin, J.M., Lefoulon, F., Fauchere, J.L., Delagrange, P., Canet, E., & Boutin, J.A. (2000). Identification of the melatonin-binding site MT3 as the quinone reductase 2. Journal of Biology and Chemistry 275, 31311–31317.Google Scholar
Nosjean, O., Nicolas, J.P., Klupsch, F., Delagrange, P., Canet, E., & Boutin, J.A. (2001). Comparative pharmacological studies of melatonin receptors: MT1, MT2 and MT3/QR2. Tissue distribution of MT3/QR2. Biochemical Pharmacology 61, 1369–1379.Google Scholar
Oishi, T. & Matsumoto, M. (1996). Circadian mitotic rhythm in the corneal epithelium of Japanese quail: Intraocular initiation of rhythm. In Circadian Clock and Zeitgebers, ed. Hiroshige, T. & Honma, K., pp. 45–54. Sapporo: Hokkaido University.
Osborne, N.N., Chidlow, G., Nash, M.S., & Wood, J.P. (1999). The potential of neuroprotection in glaucoma treatment. Current Opinion in Ophthalmology 10, 82–92.Google Scholar
Pandi-Perumal, S.R., Srinivasan, V., Maestroni, G.J.M., Cardinali, D.P., Poeggeler, B., & Hardeland, R. (2006). Melatonin: Nature's most versatile biological signal? The Federation of European Biochemical Societies Journal 273, 2813–2838.Google Scholar
Pandi-Perumal, S.R., Zisapel, N., Srinivasan, V., & Cardinali, D.P. (2005). Melatonin and sleep in aging population. Experimental Gerontology 40, 911–925.Google Scholar
Peres, M.F. (2005). Melatonin, the pineal gland and their implications for headache disorders. Cephalalgia 25, 403–411.Google Scholar
Peres, M.F., Masruha, M.R., Zukerman, E., Moreira-Filho, C.A., & Cavalheiro, E.A. (2006). Potential therapeutic use of melatonin in migraine and other headache disorders. Expert Opinions in Investigative Drugs 15, 367–375.Google Scholar
Peres, M.F., Sanchez, D.R., Seabra, M.L., Tufik, S., Abucham, J., Cipolla-Neto, J., Silberstein, S.D., & Zukerman, E. (2001). Hypothalamic involvement in chronic migraine. Journal of Neurology, Neurosurgery and Psychiatry 71, 747–751.Google Scholar
Peres, M.F., Zukerman, E., Da Cunha, T.F., Moreira, F.R., & Cipolla-Neto, J. (2004). Melatonin, 3 mg, is effective for migraine prevention. Neurology 63, 757.Google Scholar
Peters, J.L. & Cassone, V.M. (2005). Melatonin regulates circadian electroretinogram rhythms in a dose- and time-dependent fashion. Journal of Pineal Research 38, 209–215.Google Scholar
Petit, L., Lacroix, I., de Coppet, P., Strosberg, A.D., & Jockers, R. (1999). Differential signaling of human Mel1a and Mel1b melatonin receptors through the cyclic guanosine 3′-5′-monophosphate pathway. Biochemical Pharmacology 58, 633–639.Google Scholar
Pierce, M.E. & Besharse, J.C. (1985). Circadian regulation of retinomotor movements. I. Interaction of melatonin and dopamine in the control of cone length. Journal of General Physiology 86, 671–689.Google Scholar
Pintor, J., Martin, L., Pelaez, T., Hoyle, C.H., & Peral, A. (2001). Involvement of melatonin MT3 receptors in the regulation of intraocular pressure in rabbits. European Journal of Pharmacology 416, 251–254.Google Scholar
Rager, G. (1979). The cellular origin of the b-wave in the electroretinogram—a developmental approach. Journal of Comparative Neurology 188, 225–244.Google Scholar
Rea, M.S., Bullough, J.D, & Figueiro, M.G. (2001). Human melatonin suppression by light: A case for scotopic efficiency. Neuroscience Letters 299, 45–48.Google Scholar
Redman, J., Armstrong, S., & Ng, K.T. (1983). Free-running activity rhythms in the rat: Entrainment by melatonin. Science 219, 1089–1091.Google Scholar
Reiter, R.J (1980). The pineal and its hormones in the control of reproduction in mammals. Endocrinology Review 1, 109–131.Google Scholar
Reiter, R.J. (2003). Melatonin: Clinical relevance. Best Practice and Research. Clinical Endocrinology and Metabolism 17, 273–285.Google Scholar
Reiter, R.J. & Tan, D.X. (2002). Melatonin: An antioxidant in edible plants. Annuals of the New York Academy of Sciences 957, 341–344.Google Scholar
Reiter, R.J., Tan, D.X., & Maldonado, M.D. (2005). Melatonin as an antioxidant: Physiology versus pharmacology. Journal of Pineal Research 39, 215–216.Google Scholar
Reppert, S.M., Godson, C., Mahle, C.D., Weaver, D.R., Slaugenhaupt, S.A., & Gusella, J.F. (1995). Molecular characterization of a second melatonin receptor expressed in human retina and brain: The Mel1b melatonin receptor. Proceedings of the National Academy of Science USA 92, 8734–8738.Google Scholar
Reppert, S.M., Weaver, D.R., & Ebisawa, T. (1994). Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron 13, 1177–1185.Google Scholar
Ribelayga, C., Wang, Y., & Mangel, S.C. (2004). A circadian clock in the fish retina regulates dopamine release via activation of melatonin receptors. Journal of Physiology 554, 467–482.Google Scholar
Ritch, R. (2000). Neuroprotection: Is it already applicable to glaucoma therapy? Current Opinions in Ophthalmology 11, 78–84.Google Scholar
Rodriguez, I.R., Mazuruk, K., Schoen, T.J., & Chader, G.J. (1994). Structural analysis of the human hydroxyindole-O-methyltransferase gene. Presence of two distinct promoters. Journal of Biology and Chemistry 269, 31969–31977.Google Scholar
Roka, F., Brydon, L., Waldhoer, M., Strosberg, A.D., Freissmuth, M., Jockers, R., & Nanoff, C. (1999). Tight association of the human Mel1a-melatonin receptor and Gi: Precoupling and constitutive activity. Molecular Pharmacology 56, 1014–1024.Google Scholar
Rufiange, M., Dumont, M., & Lachapelle, P. (2002). Correlating retinal function with melatonin secretion in subjects with an early or late circadian phase. Investigative Ophthalmology and Visual Science 43, 2491–2499.Google Scholar
Sakamoto, K., Liu, C., & Tosini, G. (2004). Circadian rhythms in the retina of rats with photoreceptor degeneration. Journal of Neurochemistry 90, 1019–1024.Google Scholar
Sakamoto, K., Oishi, K., Shiraishi, M., Hamano, S., Otsuka, H., Miyake, Y., & Ishida, N. (2000). Two circadian oscillatory mechanisms in the mammalian retina. Neuroreport 11, 3995–3997.Google Scholar
Samples, J.R., Krause, G., & Lewy, A.J. (1988). Effect of melatonin on intraocular pressure. Current Eye Research 7, 649–653.Google Scholar
Sasaki, M., Masuda, A., & Oishi, T. (1995). Circadian rhythms of corneal mitotic rate, retinal melatonin and immunoreactive visual pigments, and the effects of melatonin on the rhythms in the Japanese quail. Journal of Comparative Physiology [A] 176, 465–471.Google Scholar
Savaskan, E., Wirz-Justice, A., Olivieri, G., Pache, M., Krauchi, K., Brydon, L., Jockers, R., Muller-Spahn, F., & Meyer, P. (2002). Distribution of melatonin MT1 receptor immunoreactivity in human retina. Journal of Histochemistry and Cytochemistry 50, 519–526.Google Scholar
Scheer, F.A., Van Montfrans, G.A., Van Someren, E.J., Mairuhu, G., & Buijs, R.M. (2004). Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension 43, 192–197.Google Scholar
Scher, J., Wankiewicz, E., Brown, G.M., & Fujieda, H. (2002). MT1 melatonin receptor in the human retina: Expression and localization. Investigative Ophthalmology and Visual Science 43, 889–897.Google Scholar
Scher, J., Wankiewicz, E., Brown, G.M., & Fujieda, H. (2003). AII amacrine cells express the MT1 melatonin receptor in human and macaque retina. Experimental Eye Research 77, 375–382.Google Scholar
Sekaran, S., Foster, R.G, Lucas, R.J., & Hankins, M.W. (2003). Calcium imaging reveals a network of intrinsically light-sensitive inner-retinal neurons. Current Biology 13, 1290–1298.Google Scholar
Serle, J.B., Wang, R.F., Peterson, W.M, Plourde, R., & Yerxa, B.R. (2004). Effect of 5-MCA-NAT, a putative melatonin MT3 receptor agonist, on intraocular pressure in glaucomatous monkey eyes. Journal of Glaucoma 13, 385–388.Google Scholar
Siu, A.W., Reiter, R.J, & To, C.H. (1999). Pineal indoleamines and vitamin E reduce nitric oxide-induced lipid peroxidation in rat retinal homogenates. Journal of Pineal Research 27, 122–128.Google Scholar
Srinivasan, V., Maestroni, G.J.M., Cardinali, D.P., Esquifino, A.I., Pandi-Perumal, S.R., & Miller, S.C. (2005a). Melatonin, immune function and aging. Immunity and Ageing 2, 17.Google Scholar
Srinivasan, V., Pandi-Perumal, S.R., Maestroni, G.J., Esquifino, A.I., Hardeland, R., & Cardinali, D.P. (2005b). Role of melatonin in neurodegenerative diseases. Neurotoxicity Research 7, 293–318.Google Scholar
Srinivasan, V., Smits, G., Kayumov, L., Pandi-Perumal, S.R., Cardinali, D.P., & Thorpy, M.J. (2006). Melatonin in circadian rhythm sleep disorders. In Neuroendocrine Correlates of Sleep/Wakefulness, ed. Cardinali, D.P. & Pandi-Perumal, S.R., pp. 269–294. New York: Springer.
Strettoi, E. & Masland, R.H. (1996). The number of unidentified amacrine cells in the mammalian retina. Proceedings of the National Academy of Science USA 93, 14906–14911.Google Scholar
Terman, J.S., Reme, C.E., & Terman, M. (1993). Rod outer segment disk shedding in rats with lesions of the suprachiasmatic nucleus. Brain Research 605, 256–264.Google Scholar
Thomas, K.B., Brown, A.D., & Iuvone, P.M. (1998). Elevation of melatonin in chicken retina by 5-hydroxytryptophan: Differential light/dark responses. Neuroreport 9, 4041–4044.Google Scholar
Thompson, C.L., Selby, C.P., Partch, C.L., Plante, D.T., Thresher, R.J., Araujo, F., & Sancar, A. (2004). Further evidence for the role of cryptochromes in retinohypothalamic photoreception/phototransduction. Brain Research, Molecular Brain Research 122, 158–166.Google Scholar
Tilden, A.R., Becker, M.A., Amma, L.L., Arciniega, J., & McGaw, A.K. (1997). Melatonin production in an aerobic photosynthetic bacterium: An evolutionarily early association with darkness. Journal of Pineal Research 22, 102–106.Google Scholar
Toglia, J.U. (1986). Is migraine due to a deficiency of pineal melatonin? Italian Journal of Neurological Science 7, 319–323.Google Scholar
Tosini, G. & Dirden, J.C. (2000). Dopamine inhibits melatonin release in the mammalian retina: In vitro evidence. Neuroscience Letters 286, 119–122.Google Scholar
Tosini, G. & Fukuhara, C. (2002). The mammalian retina as a clock. Cell Tissue Research 309, 119–126.Google Scholar
Tosini, G. & Menaker, M. (1996). Circadian rhythms in cultured mammalian retina. Science 272, 419–421.Google Scholar
Tosini, G. & Menaker, M. (1998). The clock in the mouse retina: Melatonin synthesis and photoreceptor degeneration. Brain Research 789, 221–228.Google Scholar
Tyni, T., Johnson, M., Eaton, S., Pourfarzam, M., Andrews, R., & Turnbull, D.M. (2002). Mitochondrial fatty acid beta-oxidation in the retinal pigment epithelium. Pediatric Research 52, 595–600.Google Scholar
Uchida, K. & Iuvone, P.M. (1999). Intracellular Ca2+ concentrations in cultured chicken photoreceptor cells: Sustained elevation in depolarized cells and the role of dihydropyridine-sensitive Ca2+ channels. Molecular Vision 5, 1.Google Scholar
van Den, T.M., Buijs, R.M., Ruijter, J.M., Delagrange, P., Spanswick, D., & Hermes, M.L. (2001). Melatonin generates an outward potassium current in rat suprachiasmatic nucleus neurones in vitro independent of their circadian rhythm. Neuroscience 107, 99–108.Google Scholar
von Gall, C., Stehle, J.H., & Weaver, D.R. (2002). Mammalian melatonin receptors: Molecular biology and signal transduction. Cell Tissue Research 309, 151–162.Google Scholar
Wan, Q., Man, H.Y., Liu, F., Braunton, J., Niznik, H.B., Pang, S.F., Brown, G.M., & Wang, Y.T. (1999). Differential modulation of GABAA receptor function by Mel1a and Mel1b receptors. National Neuroscience 2, 401–403.Google Scholar
White, M.P. & Fisher, L.J. (1989). Effects of exogenous melatonin on circadian disc shedding in the albino rat retina. Vision Research 29, 167–179.Google Scholar
Wiechmann, A.F. & Rada, J.A. (2003). Melatonin receptor expression in the cornea and sclera. Experimental Eye Research 77, 219–225.Google Scholar
Wiechmann, A.F., Vrieze, M.J., Dighe, R., & Hu, Y. (2003). Direct modulation of rod photoreceptor responsiveness through a Mel(1c) melatonin receptor in transgenic Xenopus laevis retina. Investigative Ophthalmology and Visual Science 44, 4522–4531.Google Scholar
Witkovsky, P., Veisenberger, E., LeSauter, J., Yan, L., Johnson, M., Zhang, D.Q., McMahon, D., & Silver, R. (2003). Cellular location and circadian rhythm of expression of the biological clock gene Period 1 in the mouse retina. Journal Neuroscience 23, 7670–7676.Google Scholar
Witt-Enderby, P.A., Bennett, J., Jarzynka, M.J., Firestine, S., & Melan, M.A. (2003). Melatonin receptors and their regulation: Biochemical and structural mechanisms. Life Sciences 72, 2183–2198.Google Scholar
Yi, C., Pan, X., Yan, H., Guo, M., & Pierpaoli, W. (2005). Effects of melatonin in age-related macular degeneration. Annuals of the New York Academy of Science 1057, 384–392.Google Scholar
Zaunreiter, M., Brandstatter, R., & Goldschmid, A. (1998). Evidence for an endogenous clock in the retina of rainbow trout: I. Retinomotor movements, dopamine and melatonin. Neuroreport 9, 1205–1209.Google Scholar
Zawilska, J.B. (1992). Melatonin in vertebrate retina: Biosynthesis, receptors and functions. Polish Journal of Pharmacology and Pharmacy 44, 627–654.Google Scholar
Zurak, N. (1997). Role of the suprachiasmatic nucleus in the pathogenesis of migraine attacks. Cephalalgia 17, 723–728.Google Scholar