Fatp1 Deficiency Affects Retinal Light Response and Dark Adaptation, and Induces Age-Related Alterations 英文参考文献.docVIP

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Fatp1 Deficiency Affects Retinal Light Response and Dark Adaptation, and Induces Age-Related Alterations 英文参考文献.doc

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Fatp1 Deficiency Affects Retinal Light Response and Dark Adaptation, and Induces Age-Related Alterations 英文参考文献

Fatp1DeficiencyAffectsRetinalLightResponseandDark Adaptation,andInducesAge-RelatedAlterations KarimChekroud1,LaurentGuillou1,StephaneGre′goire2,GillesDucharme3,EmilieBrun1, ChantalCazevieille4,LionelBretillon2,ChristianP.Hamel1,PhilippeBrabet1*.,MarieO.Pequignot1*. 1InsermU1051,InstituteforNeurosciencesofMontpellier,CHUStEloi,Montpellier,France,2INRA,EyeandNutritionResearchGroup,Dijon,France,3CNRSUMR5149, InstitutdeMathe′matiques etdeMode′lisation deMontpellier,France,4CRIC/IURC641,Montpellier,France Abstract FATP1isinvolvedinlipidtransportintocellsandinintracellularlipidmetabolism.Weshowedpreviouslythatthisprotein interactswithandinhibitsthelimiting-stepisomeraseofthevisualcycleRPE65.Here,weaimedtoanalyzetheeffectof Fatp1-deficiencyinvivoonthevisualcycle,structureandfunction,andonretinalaging.AmongtheFatpfamilymembers, weobserved thatonly Fatp1 and4 areexpressedin thecontrol retina,in both theneuroretinaand theretinalpigment epithelium.Intheneuroretina,Fatp1ismostlyexpressedinphotoreceptors.InyoungadultFatp12/2mice,Fatp4expression +/+ wasunchangedinretinalpigmentepitheliumandreducedtwo-foldintheneuroretinaascomparedtoFatp1 mice.The Fatp12/2 mice had a preserved retinal structure but a decreased electroretinogram response to light. These mice also displayedadelayedrecoveryoftheb-waveamplitudeafterbleaching,however,visualcyclespeedwasunchanged,and bothretinalpigmentepitheliumandphotoreceptorspresentedthesamefattyacidpatterncomparedtocontrols.In2year- old Fatp12/2 mice, transmission electron microscopy studies showed specific abnormalities in the retinas comprising choroid vascularization anomalies and thickening of the Bruch membrane with material deposits, and sometimes local disorganization of the photoreceptor outer segments. These anomalies lead us to speculate that the absence of FATP1 acceleratestheagingprocess. Citation:ChekroudK,GuillouL,Gre′goireS,DucharmeG,BrunE,etal.(2012)Fatp1DeficiencyAffectsRetinalLightResponseandDarkAdaptation,andInduce