BMP7 Gene Transfer via Gold Nanoparticles into Stroma Inhibits Corneal Fibrosis In Vivo. e66434

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 pol...

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Veröffentlicht in:PloS one 2013-06, Vol.8 (6)
Hauptverfasser: Tandon, Ashish, Sharma, Ajay, Rodier, Jason T, Klibanov, Alexander M, Rieger, Frank G, Mohan, Rajiv R
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Sprache:eng
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Zusammenfassung: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 [ alpha -smooth muscle actin ( alpha SMA), 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 (2104 gene copies/ug DNA). Localized BMP7 gene therapy showed a significant corneal haze decrease (1.68 plus or minus 0.31 compared to 3.2 plus or minus 0.43 in control corneas; p
ISSN:1932-6203
DOI:10.1371/journal.pone.0066434