BMP7 Gene Transfer via Gold Nanoparticles into Stroma Inhibits Corneal Fibrosis In Vivo
- Publication Date
- June 14, 2013
- Journal
- PLOS ONE
- Authors
- Ashish Tandon, Ajay Sharma, Jason T. Rodier, Alexander M. Klibanov, et al
- Volume
- 8
- Issue
- 6
- Pages
- e66434
- DOI
- https://dx.plos.org/10.1371/journal.pone.0066434
- Publisher URL
- http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0066434
- PubMed
- http://www.ncbi.nlm.nih.gov/pubmed/23799103
- PubMed Central
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682981
- Europe PMC
- http://europepmc.org/abstract/MED/23799103
- Web of Science
- 000320363300082
- Scopus
- 84879127594
- Mendeley
- http://www.mendeley.com/research/bmp7-gene-transfer-via-gold-nanoparticles-stroma-inhibits-corneal-fibrosis-vivo
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Mendeley | Further Information
{"title"=>"BMP7 Gene Transfer via Gold Nanoparticles into Stroma Inhibits Corneal Fibrosis In Vivo", "type"=>"journal", "authors"=>[{"first_name"=>"Ashish", "last_name"=>"Tandon", "scopus_author_id"=>"36633194900"}, {"first_name"=>"Ajay", "last_name"=>"Sharma", "scopus_author_id"=>"55605770173"}, {"first_name"=>"Jason T.", "last_name"=>"Rodier", "scopus_author_id"=>"55486848000"}, {"first_name"=>"Alexander M.", "last_name"=>"Klibanov", "scopus_author_id"=>"7102686277"}, {"first_name"=>"Frank G.", "last_name"=>"Rieger", "scopus_author_id"=>"14820763500"}, {"first_name"=>"Rajiv R.", "last_name"=>"Mohan", "scopus_author_id"=>"7201547556"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"369140313", "sgr"=>"84879127594", "issn"=>"19326203", "pmid"=>"23799103", "scopus"=>"2-s2.0-84879127594", "doi"=>"10.1371/journal.pone.0066434", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"ca687312-36aa-3be3-a14f-32e69e2657ee", "abstract"=>"This study examined the effects of BMP7 gene transfer on corneal wound healing and fibrosis inhibition in vivo using a rabbit model. Corneal haze in rabbits was produced with the excimer laser performing -9 diopters photorefractive keratectomy. BMP7 gene was introduced into rabbit keratocytes by polyethylimine-conjugated gold nanoparticles (PEI2-GNPs) transfection solution single 5-minute topical application on the eye. Corneal haze and ocular health in live animals was gauged with stereo- and slit-lamp biomicroscopy. The levels of fibrosis [α-smooth muscle actin (αSMA), F-actin and fibronectin], immune reaction (CD11b and F4/80), keratocyte apoptosis (TUNEL), calcification (alizarin red, vonKossa and osteocalcin), and delivered-BMP7 gene expression in corneal tissues were quantified with immunofluorescence, western blotting and/or real-time PCR. Human corneal fibroblasts (HCF) and in vitro experiments were used to characterize the molecular mechanism mediating BMP7's anti-fibrosis effects. PEI2-GNPs showed substantial BMP7 gene delivery into rabbit keratocytes in vivo (2×10(4) gene copies/ug DNA). Localized BMP7 gene therapy showed a significant corneal haze decrease (1.68±0.31 compared to 3.2±0.43 in control corneas; p<0.05) in Fantes grading scale. Immunostaining and immunoblot analyses detected significantly reduced levels of αSMA (46±5% p<0.001) and fibronectin proteins (48±5% p<0.01). TUNEL, CD11b, and F4/80 assays revealed that BMP7 gene therapy is nonimmunogenic and nontoxic for the cornea. Furthermore, alizarin red, vonKossa and osteocalcin analyses revealed that localized PEI2-GNP-mediated BMP7 gene transfer in rabbit cornea does not cause calcification or osteoblast recruitment. Immunofluorescence of BMP7-transefected HCFs showed significantly increased pSmad-1/5/8 nuclear localization (>88%; p<0.0001), and immunoblotting of BMP7-transefected HCFs grown in the presence of TGFβ demonstrated significantly enhanced pSmad-1/5/8 (95%; p<0.001) and Smad6 (53%, p<0.001), and decreased αSMA (78%; p<0.001) protein levels. These results suggest that localized BMP7 gene delivery in rabbit cornea modulates wound healing and inhibits fibrosis in vivo by counter balancing TGFβ1-mediated profibrotic Smad signaling.", "link"=>"http://www.mendeley.com/research/bmp7-gene-transfer-via-gold-nanoparticles-stroma-inhibits-corneal-fibrosis-vivo", "reader_count"=>25, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Student > Doctoral Student"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>5}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Student > Doctoral Student"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>5}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Unspecified"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>6, "Veterinary Science and Veterinary Medicine"=>1, "Chemistry"=>5}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Chemistry"=>{"Chemistry"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Environmental Science"=>{"Environmental Science"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"India"=>1}, "group_count"=>0}CrossRef
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Scopus | Further Information
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Relative Metric
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