Gene Transfer Using Micellar Nanovectors Inhibits Choroidal Neovascularization In Vivo 英文参考文献.docVIP

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Gene Transfer Using Micellar Nanovectors Inhibits Choroidal Neovascularization In Vivo 英文参考文献.doc

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Gene Transfer Using Micellar Nanovectors Inhibits Choroidal Neovascularization In Vivo 英文参考文献

GeneTransferUsingMicellarNanovectorsInhibits ChoroidalNeovascularizationInVivo AyaIriyama1,2*,MakotoOba3,TakehikoIshii4,NobuhiroNishiyama5,KazunoriKataoka4,5,6 ,Yasuhiro Tamaki2,YasuoYanagi2 1Tokyo Metropolitan Geriatric Hospital, Itabashi, Tokyo, Japan, 2Department of Ophthalmology, University of Tokyo School of Medicine, Bunkyo, Tokyo, Japan, 3DepartmentofClinicalVascularRegeneration,GraduateSchoolofMedicine,TheUniversityofTokyo,Bunkyo,Tokyo,Japan,4DepartmentofBioengineering,Graduate SchoolofEngineering,TheUniversityofTokyo,Bunkyo,Tokyo,Japan,5CenterforDiseaseBiologyandIntegrativeMedicine,GraduateSchoolofMedicine,TheUniversity ofTokyo,Bunkyo,Tokyo,Japan,6DepartmentofMaterialsEngineering,GraduateSchoolofEngineering,TheUniversityofTokyo,Bunkyo,Tokyo,Japan Abstract Purpose:Age-relatedmaculardegenerationcausedbychoroidalneovascularization(CNV)remainsdifficulttobetreated despite the recent advent of several treatment options. In this study, we investigated the in vivo angiogenic control by intravenousinjectionofpolyioncomplex(PIC)micelleencapsulatingplasmidDNA(pDNA)usingamiceCNVmodel. Methods: The transfection efficiency of the PIC micelle was investigated using the laser-induced CNV in eight-week-old maleC57BJ/6mice.Firstly,eachmousereceivedintravenousinjectionofmicelleencapsulatingpDNAofYellowFluorescent Protein(pYFP)ondays1,3and5.TheexpressionofYFPwasanalyzedusingfluoresceinmicroscopyandwesternblotting analysis.Inthenextexperiments,eachmousereceivedintravenousinjectionofmicelleencapsulatingpDNAofsolubleFms- like tyrosine kinase-1 (psFlt-1) 1,3 and 5 days after the induction of CNV and the CNV lesion was analyzed by choroidal flatmountsonday7. Results: Fluoresceinmicroscopy andwestern blottinganalysis revealedthat theexpressionof YFPwasconfirmed inthe CNVareaafterinjectionofthePICmicelle,buttheexpressionwasnotdetectedneitherinmicethatreceivednakedpDNA nor those without CNV. Furthermore, the CNV area in the mice that received intravenous injection of the psFlt-1-