Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1

Jikui Shen, R. Samul, Raquel Formica, H. Akiyama, H. Liu, Y. Saishin, S. F. Hackett, S. Zinnen, K. Kossen, K. Fosnaugh, C. Vargeese, A. Gomez, K. Bouhana, R. Aitchison, P. Pavco, Peter A Campochiaro

Research output: Contribution to journalArticle

Abstract

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 1.0μg of Sirna-027 reduced retinal NV by 32% compared to fellow eyes treated with 1.0μg 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.

Original languageEnglish (US)
Pages (from-to)225-234
Number of pages10
JournalGene Therapy
Volume13
Issue number3
DOIs
StatePublished - Feb 2006

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Keywords

  • Age-related macular degeneration
  • Angiogenesis
  • Choroidal neovascularization
  • Diabetic retinopathy
  • Ischemic retinopathy
  • Retinal neovascularization
  • Small interfering RNA

ASJC Scopus subject areas

  • Genetics

Cite this

Shen, J., Samul, R., Formica, R., Akiyama, H., Liu, H., Saishin, Y., Hackett, S. F., Zinnen, S., Kossen, K., Fosnaugh, K., Vargeese, C., Gomez, A., Bouhana, K., Aitchison, R., Pavco, P., & Campochiaro, P. A. (2006). Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1. Gene Therapy, 13(3), 225-234. https://doi.org/10.1038/sj.gt.3302641