Melanopsin-Containing Retinal Ganglion Cells: Architecture, Projections, and Intrinsic Photosensitivity

Science, Journal Year: 2002, Volume and Issue: 295(5557), P. 1065 - 1070

Published: Feb. 8, 2002

The primary circadian pacemaker, in the suprachiasmatic nucleus (SCN) of mammalian brain, is photoentrained by light signals from eyes through retinohypothalamic tract. Retinal rod and cone cells are not required for photoentrainment. Recent evidence suggests that entraining photoreceptors retinal ganglion (RGCs) project to SCN. visual pigment this photoreceptor may be melanopsin, an opsin-like protein whose coding messenger RNA found a subset RGCs. By cloning rat melanopsin generating specific antibodies, we show present cell bodies, dendrites, proximal axonal segments In mice heterozygous tau-lacZ targeted gene locus, β-galactosidase–positive RGC axons projected SCN other brain nuclei involved photoentrainment or pupillary reflex. Rat RGCs exhibited intrinsic photosensitivity invariably expressed melanopsin. Hence, most likely phototransducing set clock initiate non–image-forming functions.

Language: Английский

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An action spectrum for melatonin suppression: evidence for a novel non‐rod, non‐cone photoreceptor system in humans

The Journal of Physiology, Journal Year: 2001, Volume and Issue: 535(1), P. 261 - 267

Published: Aug. 1, 2001

1 Non-image forming, irradiance-dependent responses mediated by the human eye include synchronisation of circadian axis and suppression pineal melatonin production. The retinal photopigment(s) transducing these light in humans have not been characterised. 2 Using ability to suppress nocturnal production, we aimed investigate its spectral sensitivity produce an action spectrum. Melatonin was quantified 22 volunteers 215 exposure trials using monochromatic (30 min pulse administered at time (CT) 16-18) different wavelengths (λmax 424, 456, 472, 496, 520 548 nm) irradiances (0.7-65.0 μW cm−2). 3 At each wavelength, plasma increased with increasing irradiance. Irradiance-response curves (IRCs) were fitted generated half-maximal (IR50) corrected for lens filtering used construct 4 resulting spectrum showed unique short-wavelength very from classical scotopic photopic visual systems. lack fit (r2 < 0.1) our published rod cone absorption spectra precluded photoreceptors having a major role. Cryptochromes also had poor data. Fitting series Dartnall nomograms rhodopsin-based photopigments over λmax range 420-480 nm that rhodopsin templates between 457 462 data well (r2≥ 0.73). Of these, best template 459 (r2= 0.74). 5 Our strongly support primary role novel photopigment light-induced provide first direct evidence non-rod, non-cone photoreceptive system humans.

Language: Английский

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Melanopsin and rod–cone photoreceptive systems account for all major accessory visual functions in mice

Nature, Journal Year: 2003, Volume and Issue: 424(6944), P. 75 - 81

Published: June 15, 2003

Language: Английский

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Measuring and using light in the melanopsin age

Trends in Neurosciences, Journal Year: 2013, Volume and Issue: 37(1), P. 1 - 9

Published: Nov. 25, 2013

•Photoreceptive retinal ganglion cells (ipRGCs) regulate behavior and physiology.•ipRGCs use melanopsin-dependent intrinsic light responses rod/cone inputs.•The relative contribution of each photoreceptor to evoked is not fully understood.•A method for quantifying presented that accounts complex photoreceptive inputs.•Guidance those designing architectural therapeutic lighting provided. Light a potent stimulus regulating circadian, hormonal, behavioral systems. In addition, therapy effective certain affective disorders, sleep problems, circadian rhythm disruption. These biological effects are influenced by distinct in the eye, melanopsin-containing intrinsically photosensitive (ipRGCs), addition conventional rods cones. We summarize neurophysiology this newly described sensory pathway consider implications measurement, production, application light. A new light-measurement strategy taking account inputs these non-visual proposed researchers, simple suggestions artificial/architectural provided regulatory authorities, manufacturers, designers, engineers. During past three decades, empirical evidence has demonstrated many aspects human physiology illumination [1Aschoff J. Biological Rhythms (Handbook Behavioral Neurobiology No. 4). Plenum, 1981Google Scholar, 2Wurtman R.J. et al.The Medical Effects Light. The New York Academy Sciences, 1985Google 3Wetterberg L. Man. Pergamon Press, 1993Google 4Lam R.W. Beyond Seasonal Affective Disorder: Treatment SAD non-SAD Disorders. American Psychiatric 1996Google Scholar]. Such originate eye but separate from other vision insofar as they unrelated particular spatial patterns exposure, can survive even some blind subjects. Consequently, types have been commonly referred non-image-forming or non-visual. catch-all terms encompass wide array response types. most influential light-induced phase resetting endogenous clocks. Because rhythmicity feature nearly every physiological, metabolic, system, phenomenon brings processes under indirect control. this, term come growing list more acute together ensure day-like physiological state. Thus, example, constricts pupil, suppresses pineal melatonin increases heart rate core body temperature, stimulates cortisol acts neurophysiological stimulant (increasing subjective objective measures alertness psychomotor reaction time, reducing lapses attention). Appreciation basic biology led development number applications. shown anti-depressant properties, particularly treatment seasonal disorder (SAD) its subclinical variant sSAD [3Wetterberg Appropriately timed exposure also developed circadian-rhythm disorders disruption associated with jetlag, shift work, space flight. Finally, explored non-seasonal depression, menstrual-cycle-related bulimia nervosa, cognitive fatigue problems senile dementia, chemotherapy, traumatic brain injury 5Tuunainen A. al.Light depression.Cochrane Database Syst. Rev. 2004; 2: 1-83Google 6J. Biol. Rhythms. 2005; 20: 279-386Crossref PubMed Scopus (177) Google on evolved over millennia which environmental reliable indicator time day. advent electrical disrupted relationship, now reflecting personal tastes social pressures. It important therefore incorporated into considerations design. one might ask what extent given replicates natural daylight; how could be employed minimize deleterious shiftwork while promoting safety; optimized. industry academic researchers started address [7CIE Ocular Lighting Human Physiology Behaviour. Commission Internationale de l'Éclairage, 2009Google 8IES Health: An Overview Impact Optical Radiation Visual, Circadian, Neuroendocrine Neurobehavioural Responses. Illuminating Engineering Society North America, 2008Google 9DIN Physics – Part 100: Non-visual Beings Quantities, Symbols Action Spectra. Deutsches Institut fur Normung, Progress endeavors, however, first requires appropriate quantification impacts behavior. There two broad categories measurement techniques: radiometry photometry [10DiLaura D.L. al.Lighting Handbook. Reference Application.10th ed. 2011Google Radiometry based characterizing physical properties wavelength energy. radiometer quantifies radiant power defined bandwidth electromagnetic Photometry specialized branch takes fact photoreceptors equally sensitive at all wavelengths. photometer uses filters weight detector different wavelengths according spectral sensitivity an aspect vision. Most commercially available photometers weighting function termed photopic luminous efficiency (or Vλ), reflects long- middle-wavelength-sensitive cones [11CIE l'Éclairage Proceedings, 1924, Cambridge University Press1926Google Depending geometric interest, intensity (units lumens/sr candelas, cd), luminance (cd/m2), illuminance (lm/m2 lux) determined output devices. Between 1980 2000, great majority studies endocrine, behavioral, quantified stimuli (lux) lux meters were readily inexpensive because tool choice photographic professions. Two related branches investigation since practice inadequate. First, during last decade it was discovered whereas capacity retina dominated cones, few neurons (retinal cells) directly [12Berson D.M. al.Phototransduction set clock.Science. 2002; 295: 1070-1073Crossref (2514) 13Hattar S. al.Melanopsin-containing cells: architecture, projections, photosensitivity.Science. 1065-1070Crossref (1935) achieve through expression melanopsin, opsin photopigment [14Provencio I. al.Melanopsin: melanophores, brain, eye.Proc. Natl. Acad. Sci. U.S.A. 1998; 95: 340-345Crossref (746) 15Provencio al.A novel inner retina.J. Neurosci. 2000; 600-605Crossref 16Lucas al.Diminished pupillary reflex high irradiances melanopsin-knockout mice.Science. 2003; 299: 245-247Crossref (660) ipRGCs comprise only small fraction total cell population (1–5%, depending species estimation), project major retinorecipient parts including [17Ecker J.L. al.Melanopsin-expressing ganglion-cell photoreceptors: cellular diversity role pattern vision.Neuron. 2010; 67: 49-60Abstract Full Text PDF (459) 18Brown T.M. al.Melanopsin contributions irradiance coding thalamo-cortical visual system.PLoS 8: e1000558Crossref (186) 19Gooley J.J. origin retinohypothalamic tract.Nat. 2001; 4: 1165Crossref (443) Specific ablation abolishes responses, identifying class principal conduits photic input systemic [20Goz D. al.Targeted destruction saporin conjugate alters mouse rhythms.PLoS ONE. 2008; 3: e3153Crossref (117) 21Guler A.D. rod-cone vision.Nature. 453: 102-105Crossref (605) 22Hatori M. al.Inducible melanopsin-expressing reveals their central non-image forming responses.PLoS e2451Crossref (212) Furthermore, detect when isolated rest retina, explaining why photosensitivity survives loss functional 23Foster R.G. al.Circadian photoreception retinally degenerate (rd/rd).J. Comp. Physiol. 1991; 169: 39-50Crossref (416) 24Freedman M.S. al.Regulation mammalian non-rod, non-cone, ocular photoreceptors.Science. 1999; 284: 502-504Crossref (639) 25Lucas 505-507Crossref (432) 26Yoshimura T. al.Differences between CBA/J mice (rd/rd) normal CBA/N (+/+).J. 1994; 9: 51-60Crossref (26) 27Keeler C.E. Iris movements mice.Am. 1927; 81: 107-112Crossref 28Czeisler C.A. al.Suppression secretion patients bright light.N. Engl. Med. 1995; 332: 6-11Crossref (523) 29Gooley play roles mediating continuous humans.J. 2012; 32: 14242-14253Crossref (144) This discovery raises possibility fairly rod- cone-based Second, observations indeed very sensitivity. Ten analytic action spectra investigations selected comparisons such humans, non-human primates, rodents revealed peak short-wavelength portion visible spectrum (from 447 484 nm) 30Brainard G. al.Action regulation humans: photoreceptor.J. 21: 6405-6412PubMed 31Thapan K. al.An suppression: non-cone system 535: 261-267Crossref (993) 32Yoshimura Ebihara Spectral phase-shifts rhythms (+/+) mice.J. 1996; 178: 797-802Crossref (118) 33Lucas R. al.Characterization capable driving constriction mice.Nat. 621-626Crossref (495) 34Hankins M.W. Lucas primary humans regulated long-term nonclassical photopigment.Curr. 12: 191-198Abstract (166) 35Hattar systems accessory functions mice.Nature. 424: 75-81Crossref (929) 36Dacey primate signal colour LGN.Nature. 433: 749-754Crossref (981) 37Gamlin P.D. al.Human macaque pupil driven cells.Vision Res. 2007; 47: 946-954Crossref (439) 38Zaidi F.H. al.Short-wavelength pupillary, awareness lacking outer retina.Curr. 17: 2122-2128Abstract (252) 39Lockley S.W. direct alertness, vigilance, waking electroencephalogram humans.Sleep. 2006; 29: 161-168PubMed 40Cajochen C. al.High melatonin, thermoregulation, short light.J. Clin. Endocrinol. Metab. 90: 1311-1316Crossref (632) 41Gooley al.Spectral depend duration light.Sci. Transl. 31ra33Crossref (283) 42Revell V.L. al.Alerting wavelengths.Neurosci. Lett. 399: 96-100Crossref (130) 43Lockley 88: 4502-4505Crossref (588) 44Revell phase-advancing 270-272Crossref (85) 45Brainard G.C. mediated cone system.J. 86: 433-436Crossref (94) Scholar], divergent predicted Vλ (peak 555 nm). Taken together, data demonstrate established photometric function, lux, inadequate intended Unfortunately, date there no replacement. omission practical consequences. For absence suitable agreed makes difficult compare findings replicate experimental conditions. represents significant barrier relating laboratory applications, regulators predict impact regimes fundamental problem addressing need difficulty determining (equivalent Vλ) responses. To understand challenge necessary review ipRGCs. Melanopsin, ipRGCs, structurally phylogenetically closely opsins invertebrate rhabdomeric than rod [46Borges gene duplication unconstrained selective pressures melanopsin family evolution vertebrate regulation.PLoS 7: e52413Crossref (20) 47Nasi E. del Pilar Gomez Melanopsin-mediated light-sensing amphioxus: glimpse microvillar lineage within deuterostomia.Commun. Integr. 2009; 441-443Crossref (13) common rhodopsins, phototransduction cascade engaged results depolarization [48Hughes phototransduction: slowly emerging dark.Prog. 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Each mechanisms detection sensitivity, expressed transmission media.(i)Rods. Rod opsin, photoreceptors, shows (λmax) approximately 500 nm species. Pre-receptoral filtering shifts towards somewhat longer standard observer (507 nm).(ii)Cones. Mammalian genomes typically contain genes encoding spectrally opsins. Humans, old world S express short-wavelength-sensitive (cyanolabe), maximally ∼420 nm; M (chlorolabe; ∼535 nm); L red-shifted (erythrolabe; ∼565 [56Stockman Sharpe L.T. sensitivities middle- long-wavelength derived measurements observers known genotype.Vision 40: 1711-1737Crossref (561) Scholar]). Other mammals chlorolabe/erythrolabe distinction, single middle spectrum. differences cyanolabe pigments. rodent retinas near-ultraviolet radiation [57Jacobs G.H. al.Retinal receptors ultraviolet light.Nature. 353: 655-657Crossref (338) pre-receptoral short- medium-wavelength (∼440 545 nm, respectively).(iii)Melanopsin. indicate similarly invariant across species, λmax 480 [58Panda al.Illumination signaling pathway.Science. 307: 600-604Crossref (394) 59Qiu X. al.Induction heterologous melanopsin.Nature. 745-749Crossref (344) 60Koyanagi al.Cephalochordate melanopsin: evolutionary linkage cells.Curr. 15: 1065-1069Abstract (187) 61Torii al.Two isoforms chicken melanopsins show blue sensitivity.FEBS 581: 5327-5331Abstract (65) 62Bailes H.J. forms pigment (λmax ∼479 supporting Gq/11 Gi/o cascades.Proc. 2013; 280: 20122987Crossref (199) potential complication estimate property vivo suggestion like invertebrates, may bistable 63Melyan Z. al.Addition renders photoresponsive.Nature. 741-745Crossref (335) 64Mure L.S. al.Melanopsin-dependent nonvisual responses: bistability vivo.J. 22: 411-424Crossref (131) Bistability affords photopigments regenerate vitamin A-derived chromophore isomerized following absorption another [65Hillman P. al.Transduction bistability.Physiol. 1983; 63: 668-772Crossref (109) regeneration event produced wavelengths, receptor. Whether whether biologically relevant remain [66Mawad Van Gelder R.N. Absence potentiation murine vitro.J. 387-391Crossref (36) 67Rollag M.D. Does consequences?.J. 396-399Crossref (15) 68Papamichael simultaneous presentation red monochromatic 27: 70-78Crossref (31) either event, factor does significantly [69Enezi 'melanopic' predicts polychromatic lights.J. 2011; 26: 314-323Crossref (178) 70Brown melanopic diverse conditions.PLoS e53583Crossref (29) thus five four case non-primates) follows down

Language: Английский

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Retinal repair by transplantation of photoreceptor precursors

Nature, Journal Year: 2006, Volume and Issue: 444(7116), P. 203 - 207

Published: Nov. 1, 2006

Language: Английский

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Physiology of Circadian Entrainment

Physiological Reviews, Journal Year: 2010, Volume and Issue: 90(3), P. 1063 - 1102

Published: July 1, 2010

Mammalian circadian rhythms are controlled by endogenous biological oscillators, including a master clock located in the hypothalamic suprachiasmatic nuclei (SCN). Since period of this oscillation is ∼24 h, to keep synchrony with environment, need be entrained daily means Zeitgeber (“time giver”) signals, such as light-dark cycle. Recent advances neurophysiology and molecular biology rhythmicity allow better understanding synchronization. In review we cover several aspects mechanisms for photic entrainment mammalian rhythms, retinal sensitivity light novel photopigments well variations retina that contribute regulation physiology. Downstream from retina, examine retinohypothalamic communication through neurotransmitter (glutamate, aspartate, pituitary adenylate cyclase-activating polypeptide) interaction SCN receptors resulting signal transduction pathways neurons, putative neuron-glia interactions. Finally, describe analyze gene expression its importance mechanisms, disorders or diseases related deficits, experimental clinical treatments.

Language: Английский

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Central projections of melanopsin‐expressing retinal ganglion cells in the mouse

The Journal of Comparative Neurology, Journal Year: 2006, Volume and Issue: 497(3), P. 326 - 349

Published: May 30, 2006

Abstract A rare type of ganglion cell in mammalian retina is directly photosensitive. These novel retinal photoreceptors express the photopigment melanopsin. They send axons to suprachiasmatic nucleus (SCN), intergeniculate leaflet (IGL), and olivary pretectal (OPN), thereby contributing photic synchronization circadian rhythms pupillary light reflex. Here, we sought characterize more fully projections these cells brain. By targeting tau‐lacZ melanopsin gene locus mice, that would normally were induced express, instead, marker enzyme β‐galactosidase. Their visualized by X‐gal histochemistry or anti‐β‐galactosidase immunofluorescence. Established targets confirmed, including SCN, IGL, OPN, ventral division lateral geniculate (LGv), preoptic area, but overall widespread than previously recognized. Targets included nucleus, peri‐supraoptic subparaventricular zone hypothalamus, medial amygdala, margin habenula, posterior limitans superior colliculus, periaqueductal gray. There also weak margins dorsal nucleus. Co‐staining with cholera toxin B subunit label all afferents showed provide most input habenula much other do contribute at least some targets. Staining patterns after monocular enucleation revealed are overwhelmingly crossed except for projection which bilaterally symmetrical. J. Comp. Neurol. 497:326–349, 2006. © 2006 Wiley‐Liss, Inc.

Language: Английский

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Melanopsin cells are the principal conduits for rod–cone input to non-image-forming vision

Nature, Journal Year: 2008, Volume and Issue: 453(7191), P. 102 - 105

Published: April 23, 2008

Language: Английский

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Neural remodeling in retinal degeneration

Progress in Retinal and Eye Research, Journal Year: 2003, Volume and Issue: 22(5), P. 607 - 655

Published: June 30, 2003

Language: Английский

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Diminished Pupillary Light Reflex at High Irradiances in Melanopsin-Knockout Mice

Science, Journal Year: 2003, Volume and Issue: 299(5604), P. 245 - 247

Published: Jan. 10, 2003

In the mammalian retina, a small subset of retinal ganglion cells (RGCs) are intrinsically photosensitive, express opsin-like protein melanopsin, and project to brain nuclei involved in non–image-forming visual functions such as pupillary light reflex circadian photoentrainment. We report that mice with melanopsin gene ablated, RGCs retrograde-labeled from suprachiasmatic were no longer although their number, morphology, projections unchanged. These animals showed indistinguishable wild type at low irradiances, but high irradiances was incomplete, pattern suggests melanopsin-associated system classical rod/cone complementary function.

Language: Английский

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