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Short-Wavelength Light Sensitivity of Circadian, Pupillary, and Visual Awareness in Humans Lacking an Outer Retina

2007; Elsevier BV; Volume: 17; Issue: 24 Linguagem: Inglês

10.1016/j.cub.2007.11.034

1879-0445

F H Zaidi, Joseph T. Hull, Stuart N. Peirson, Katharina Wulff, Daniel Aeschbach, Joshua J. Gooley, George C. Brainard, Kevin Gregory-Evans, Joseph F. Rizzo, Charles A. Czeisler, F. Foster, Merrick J. Moseley, Steven W. Lockley,

Photoreceptor and optogenetics research

As the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight [1Czeisler C.A. Shanahan T.L. Klerman E.B. Martens H. Brotman D.J. Emens J.S. Klein T. Rizzo 3rd, J.F. Suppression of melatonin secretion in some blind patients by exposure to bright light.N. Engl. J. Med. 1995; 332: 6-11Crossref PubMed Scopus (532) Google Scholar, 2Ruberg F.L. Skene D.J. Hanifin J.P. Rollag M.D. English J. Arendt J. Brainard G.C. Melatonin regulation in humans with color vision deficiencies.J. Clin. Endocrinol. Metab. 1996; 81: 2980-2985Crossref PubMed Scopus (53) Google Scholar, 3Lockley S.W. Skene D.J. Tabandeh H. Bird A.C. Defrance R. Arendt J. Relationship between melatonin rhythms and visual loss in the blind.J. Clin. Endocrinol. Metab. 1997; 82: 3763-3770Crossref PubMed Scopus (279) Google Scholar, 4Freedman M.S. Lucas R.J. Soni B. von Schantz M. Munoz M. David-Gray Z. Foster R. Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors.Science. 1999; 284: 502-504Crossref PubMed Scopus (657) Google Scholar, 5Lucas R.J. Freedman M.S. Munoz M. Garcia-Fernandez J.M. Foster R.G. Regulation of the mammalian pineal by non-rod, non-cone, ocular photoreceptors.Science. 1999; 284: 505-507Crossref PubMed Scopus (440) Google Scholar, 6Brainard G.C. Hanifin J.P. Greeson J.M. Byrne B. Glickman G. Gerner E. Rollag M.D. Action spectrum for melatonin regulation in humans: Evidence for a novel circadian photoreceptor.J. Neurosci. 2001; 21: 6405-6412PubMed Google Scholar, 7Thapan K. Arendt J. Skene D.J. An action spectrum for melatonin suppression: Evidence for a novel non-rod, non-cone photoreceptor system in humans.J. Physiol. 2001; 535: 261-267Crossref PubMed Scopus (1023) Google Scholar, 8Berson D.M. Dunn F.A. Takao M. Phototransduction by retinal ganglion cells that set the circadian clock.Science. 2002; 295: 1070-1073Crossref PubMed Scopus (2591) Google Scholar, 9Hattar S. Lucas R.J. Mrosovsky N. Thompson S. Douglas R.H. Hankins M.W. Lem J. Biel M. Hofmann F. Foster R.G. Yau K.W. Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice.Nature. 2003; 424: 76-81Crossref PubMed Scopus (951) Google Scholar, 10Dacey D.M. Liao H.W. Peterson B.B. Robinson F.R. Smith V.C. Pokorny J. Yau K.W. Gamlin P.D. Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN.Nature. 2005; 433: 749-754Crossref PubMed Scopus (1016) Google Scholar, 11Foster R.G. Hankins M.W. Circadian vision.Curr. Biol. 2007; 17: R746-R751Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar]. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength (∼480 nm) blue light and remain functional in the absence of rods and cones [8Berson D.M. Dunn F.A. Takao M. Phototransduction by retinal ganglion cells that set the circadian clock.Science. 2002; 295: 1070-1073Crossref PubMed Scopus (2591) Google Scholar, 9Hattar S. Lucas R.J. Mrosovsky N. Thompson S. Douglas R.H. Hankins M.W. Lem J. Biel M. Hofmann F. Foster R.G. Yau K.W. Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice.Nature. 2003; 424: 76-81Crossref PubMed Scopus (951) Google Scholar, 10Dacey D.M. Liao H.W. Peterson B.B. Robinson F.R. Smith V.C. Pokorny J. Yau K.W. Gamlin P.D. Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN.Nature. 2005; 433: 749-754Crossref PubMed Scopus (1016) Google Scholar]. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found that short-wavelength light preferentially suppressed melatonin, reset the circadian pacemaker, and directly enhanced alertness compared to 555 nm exposure, which is the peak sensitivity of the photopic visual system. In an action spectrum for pupillary constriction, the female subject exhibited a peak spectral sensitivity (λmax) of 480 nm, matching that of the pRGCs but not that of the rods and cones. This subject was also able to correctly report a threshold short-wavelength stimulus (∼480 nm) but not other wavelengths. Collectively these data show that pRGCs contribute to both circadian physiology and rudimentary visual awareness in humans and challenge the assumption that rod- and cone-based photoreception mediate all "visual" responses to light.