Gene transfer using micellar nanovectors inhibits choroidal neovascularization in vivo.

<h4>Purpose</h4>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...

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Autores principales: Aya Iriyama, Makoto Oba, Takehiko Ishii, Nobuhiro Nishiyama, Kazunori Kataoka, Yasuhiro Tamaki, Yasuo Yanagi
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:a083abcc74214c24aa672ce024fc0d0b2021-11-18T07:33:00ZGene transfer using micellar nanovectors inhibits choroidal neovascularization in vivo.1932-620310.1371/journal.pone.0028560https://doaj.org/article/a083abcc74214c24aa672ce024fc0d0b2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22162776/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.Aya IriyamaMakoto ObaTakehiko IshiiNobuhiro NishiyamaKazunori KataokaYasuhiro TamakiYasuo YanagiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e28560 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Aya Iriyama
Makoto Oba
Takehiko Ishii
Nobuhiro Nishiyama
Kazunori Kataoka
Yasuhiro Tamaki
Yasuo Yanagi
Gene transfer using micellar nanovectors inhibits choroidal neovascularization in vivo.
description <h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.
format article
author Aya Iriyama
Makoto Oba
Takehiko Ishii
Nobuhiro Nishiyama
Kazunori Kataoka
Yasuhiro Tamaki
Yasuo Yanagi
author_facet Aya Iriyama
Makoto Oba
Takehiko Ishii
Nobuhiro Nishiyama
Kazunori Kataoka
Yasuhiro Tamaki
Yasuo Yanagi
author_sort Aya Iriyama
title Gene transfer using micellar nanovectors inhibits choroidal neovascularization in vivo.
title_short Gene transfer using micellar nanovectors inhibits choroidal neovascularization in vivo.
title_full Gene transfer using micellar nanovectors inhibits choroidal neovascularization in vivo.
title_fullStr Gene transfer using micellar nanovectors inhibits choroidal neovascularization in vivo.
title_full_unstemmed Gene transfer using micellar nanovectors inhibits choroidal neovascularization in vivo.
title_sort gene transfer using micellar nanovectors inhibits choroidal neovascularization in vivo.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/a083abcc74214c24aa672ce024fc0d0b
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AT makotooba genetransferusingmicellarnanovectorsinhibitschoroidalneovascularizationinvivo
AT takehikoishii genetransferusingmicellarnanovectorsinhibitschoroidalneovascularizationinvivo
AT nobuhironishiyama genetransferusingmicellarnanovectorsinhibitschoroidalneovascularizationinvivo
AT kazunorikataoka genetransferusingmicellarnanovectorsinhibitschoroidalneovascularizationinvivo
AT yasuhirotamaki genetransferusingmicellarnanovectorsinhibitschoroidalneovascularizationinvivo
AT yasuoyanagi genetransferusingmicellarnanovectorsinhibitschoroidalneovascularizationinvivo
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