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1、©2015.PublishedbyTheCompanyofBiologistsLtd
2、DiseaseModels&Mechanisms(2015)8,701-710doi:10.1242/dmm.020248RESEARCHARTICLEAmitochondrialtherapeuticreversesvisualdeclineinmousemodelsofdiabetesNaziaM.Alam1,2,3,AimeeA.Wong2,RobertM.Douglas4,HazelH.Szeto3and*,WilliamC.MillsIVGlenT.Prusky1,2ABSTRACTa
3、nti-vascularendothelialgrowthfactoragentsisabletoimproveDiabeticretinopathyischaracterizedbyprogressivevisionlossandthevisualfunctionin<30%ofpatients.Likewise,therapiesaimedatadvancementofretinalmicoraneurysms,edemaandangiogenesis.managingthesymptomsofmetabolicdysfunctionhaveshownUnfortunatel
4、y,managingglycemiaortargetingvascularcomplicationslimitedefficacyinslowingtheprogressionofdiabeticretinopathy;withanti-vascularendothelialgrowthfactoragentshasshowndiabeticcomplicationsdevelopin∼20%ofpatientsunderstrictonlylimitedefficacyintreatingthedeteriorationofvisionindiabeticglycemicorb
5、lood-pressurecontrol(Antonettietal.,2012).Thus,retinopathy.Inlightofgrowingevidencethatmitochondrialdysfunctionearlierdetectionofriskfordiabetesanddiabeticretinopathy,andisanindependentpathophysiologyofdiabetesanddiabeticinterventionwithnoveltherapeuticsbeforeirreversibleretinalretinopathy,we
6、investigatedwhetherselectivelytargetinganddamageoccurs,havegreatpotentialtoimprovetreatment.improvingmitochondrialdysfunctionisaviabletreatmentforvisualThereisgrowingrecognitionthatretinaldysfunction(Barberetal.,declineindiabetes.Measuresofspatialvisualbehavior,blood2005;Lyetal.,2011;Martinet
7、al.,2004;MurakamiandYoshimura,glucose,bodyweightandopticalclarityweremadeinmousemodels2013;vanDijketal.,2009)andimpairedvisualbehaviorispresentinofdiabetes.TreatmentgroupswereadministeredMTP-131,awater-humandiabeticsandinanimalmodelsbeforeretinalvascularchangessolubletetrapeptidethatselective
8、lytargetsmitochondrialcardiolipinareevident(AkimovandRentería,2012;Aungetal.,2013;Hardyandpromotesefficientelectrontransfer,eithersystemicallyorineyeetal.,1992;Jacksonetal.,2012;Kirwinetal.,2011).Thus,thedrops.Progressivevisualdeclineemergedi