title: Gene transfer using micellar nanovectors inhibits choroidal neovascularization in vivo.
abstract: OBJECTIVE
  Age-related macular degeneration caused by choroidal neovascularization (CNV) remains difficult to be treated despite the recent advent of several treatment options. In this study, we investigated the in vivo angiogenic control by intravenous injection of polyion complex (PIC) micelle encapsulating plasmid DNA (pDNA) using a mice CNV model.
  
  
  METHODS
  The transfection efficiency of the PIC micelle was investigated using the laser-induced CNV in eight-week-old male C57 BJ/6 mice. Firstly, each mouse received intravenous injection of micelle encapsulating pDNA of Yellow Fluorescent Protein (pYFP) on days 1,3 and 5. The expression of YFP was analyzed using fluorescein microscopy and western blotting analysis. In the next experiments, each mouse received intravenous injection of micelle encapsulating pDNA of soluble Fms-like tyrosine kinase-1 (psFlt-1) 1,3 and 5 days after the induction of CNV and the CNV lesion was analyzed by choroidal flatmounts on day 7.
  
  
  RESULTS
  Fluorescein microscopy and western blotting analysis revealed that the expression of YFP was confirmed in the CNV area after injection of the PIC micelle, but the expression was not detected neither in mice that received naked pDNA nor those without CNV. Furthermore, the CNV area in the mice that received intravenous injection of the psFlt-1-encapsulated PIC micelle was significantly reduced by 65% compared to that in control mice (p<0.01).
  
  
  CONCLUSIONS
  Transfection of sFlt-1 with the PIC micelle by intravenous injection to mice CNV models showed significant inhibition of CNV. The current results revealed the significant potential of nonviral gene therapy for regulation of CNV using the PIC micelle encapsulating pDNA.
authors.affiliation: Tokyo Metropolitan Geriatric Hospital, Itabashi, Tokyo, Japan. akagi-tky@umin.ac.jp
authors.forename: Aya
authors.initials: A
authors.lastname: Iriyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Oba
authors.forename: Takehiko
authors.initials: T
authors.lastname: Ishii
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yanagi
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D019793:Fluorescein / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D017075:Laser Coagulation / Q000379:methods; D008028:Light Coagulation; D008164:Luminescent Proteins / Q000378:metabolism; D008268:Macular Degeneration / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D008856:Microscopy, Fluorescence / Q000379:methods; D011108:Polymers / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; D008823:Micelles; D011108:Polymers; C054562:yellow fluorescent protein, Bacteria; D004247:DNA; D019793:Fluorescein