Secondary Post-Geniculate Involvement in Leber’s Hereditary Optic Neuropathy 英文参考文献.docVIP

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Secondary Post-Geniculate Involvement in Leber’s Hereditary Optic Neuropathy 英文参考文献.doc

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SecondaryPost-GeniculateInvolvementinLeber’s HereditaryOpticNeuropathy GiovanniRizzo1,2,KevinR.Tozer3,CaterinaTonon1,DavidManners1,ClaudiaTesta1,EmilMalucelli1, MariaLuciaValentino1,2,ChiaraLaMorgia1,2,PieroBarboni4,RuvdeepS.Randhawa3,FredN.Ross- Cisneros3,AlfredoA.Sadun3,ValerioCarelli1,2*,RaffaeleLodi1* 1Department of Biomedical and NeuroMotor Sciences (DiBiNeM), University of Bologna, Bologna, Italy, 2‘‘IRCCS Istituto delle Scienze Neurologiche’’, Bologna, Italy, 3DohenyEyeInstituteandDepartmentofOphthalmology,KeckSchoolofMedicine,UniversityofSouthernCalifornia,LosAngeles,California,UnitedStatesofAmerica, 4StudioOculisticod’Azeglio,Bologna,Italy Abstract Leber’s hereditary optic neuropathy (LHON) is characterized by retinal ganglion cell (RGC) degeneration with the preferentialinvolvementofthoseformingthepapillomacularbundle.Theopticnerveisconsideredthemainpathological target for LHON. Our aim was to investigate the possible involvement of the post-geniculate visual pathway in LHON patients.Weuseddiffusion-weightedimagingforinvivoevaluation.Meandiffusivitymapsfrom22LHONvisuallyimpaired, 11unaffectedLHONmutationcarriersand22healthysubjects weregenerated andcomparedatlevelofopticradiation (OR).Prefrontalandcerebellarwhitematterwerealsoanalyzedasinternalcontrols.Furthermore,westudiedtheopticnerve andthelateralgeniculatenucleus(LGN)inpost-mortemspecimensobtainedfromaseverecaseofLHONcomparedtoan age-matchedcontrol.Meandiffusivityvaluesofaffectedpatientswerehigherthanunaffectedmutationcarriers(P,0.05) andhealthysubjects(P,0.01)inORandnotintheotherbrainregions.IncreasedORdiffusivitywasassociatedwithboth disease duration (B=0.002; P,0.05) and lack of recovery of visual acuity (B=0.060; P,0.01). Post-mortem investigation detectedatrophy(41.9%decreaseofneuronsomasizeinthemagnocellularlayersand44.7%decreaseintheparvocellular layers) and, to a lesser extent, degeneration (28.5% decrease of neuron density in the magnocellular layers and 28.7% decreaseintheparvocellularl