Melanopsin Bistability A Flys Eye Technology in the Human Retina 英文参考文献.docVIP

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Melanopsin Bistability A Flys Eye Technology in the Human Retina 英文参考文献.doc

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Melanopsin Bistability A Flys Eye Technology in the Human Retina 英文参考文献

MelanopsinBistability:AFly’sEyeTechnologyinthe HumanRetina LudovicS.Mure1,2,Pierre-LoicCornut1,2,3,CamilleRieux1,2,EliseDrouyer1,2,PhilippeDenis1,2,3 ,Claude Gronfier1,2,HowardM.Cooper1,2 * 1DepartmentofChronobiology,INSERM,U846,StemCellandBrainResearchInstitute,Bron,France,2UniversityofLyon,LyonI,UMR-S846,Lyon,France,3Department ofOphthalmology,CHUdeLyonHopitalEdouardHerriot,Lyon,France Abstract In addition to rods and cones, the human retina contains light-sensitive ganglion cells that express melanopsin, a photopigmentwithsignaltransductionmechanismssimilartothatofinvertebraterhabdomericphotopigments(IRP).Like fly rhodopsins, melanopsin acts as a dual-state photosensitive flip-flop in which light drives both phototransduction responsesandchromophorephotoregenerationthatbestowsindependencefromtheretinoidcyclerequiredbyrodsand cones to regenerate photoresponsiveness following bleaching by light. To explore the hypothesis that melanopsin in humansexpressesthepropertiesofabistablephotopigmentinvivoweusedthepupillarylightreflex(PLR)asatoolbut withmethodsdesignedtostudyinvertebratephotoreceptors.Weshowthatthepupilonlyattainsafullystabilizedstateof constrictionafterseveralminutesoflightexposure,afeaturethatisconsistentwithtypicalIRPphotoequilibriumspectra. Wefurtherdemonstratethatpreviousexposuretolongwavelengthlightincreases,whileshortwavelengthlightdecreases the amplitude of pupil constriction, a fundamental property of IRP difference spectra. Modelling these responses to invertebratephotopigment templatesyieldstwoputativespectrafortheunderlyingR andMphotopigment stateswith peaks at 481nm and 587nm respectively. Furthermore, this bistable mechanism may confer a novel form of ‘‘photic memory’’ since information of priorlight conditions is retained andshapes subsequent responses to light. Theseresults suggest that the human retina exploits fly-like photoreceptive mechanisms that are potentially important for the modulationofnon-visualresponsestolightandhighlightsth