Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1
In this study, we used small interfering RNA (siRNA) directed against vascular endothelial growth factor receptor 1 ( vegfr1) mRNA to investigate the role of VEGFR1 in ocular neovascularization (NV). After evaluating many siRNAs, Sirna-027 was identified; it cleaved vegfr1 mRNA at the predicted site...
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Veröffentlicht in: | Gene therapy 2006-02, Vol.13 (3), p.225-234 |
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Hauptverfasser: | , , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | In this study, we used small interfering RNA (siRNA) directed against
vascular endothelial growth factor receptor 1
(
vegfr1)
mRNA to investigate the role of VEGFR1 in ocular neovascularization (NV). After evaluating many siRNAs, Sirna-027 was identified; it cleaved
vegfr1
mRNA at the predicted site and reduced its levels in cultured endothelial cells and in mouse models of retinal and choroidal neovascularization (CNV). Compared to injection of an inverted control sequence, quantitative reverse transcriptase-PCR demonstrated statistically significant reductions of 57 and 40% in
vegfr1
mRNA after intravitreous or periocular injection of Sirna-027, respectively. Staining showed uptake of 5-bromodeoxyuridine-labeled Sirna-027 in retinal cells that lasted between 3 and 5 days after intravitreous injection and was still present 5 days after periocular injection. In a CNV model, intravitreous or periocular injections of Sirna-027 resulted in significant reductions in the area of NV ranging from 45 to 66%. In mice with ischemic retinopathy, intravitreous injection of 1.0
μ
g of Sirna-027 reduced retinal NV by 32% compared to fellow eyes treated with 1.0
μ
g of inverted control siRNA. These data suggest that VEGFR1 plays an important role in the development of retinal and CNV and that targeting
vegfr1
mRNA with siRNA has therapeutic potential. |
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ISSN: | 0969-7128 1476-5462 |
DOI: | 10.1038/sj.gt.3302641 |