May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Non-Targeted siRNA Suppress Angiogenesis in the Cornea, Dermis and Hind Limb
Author Affiliations & Notes
  • M. Nozaki
    University of Kentucky, Lexington, Kentucky
    Ophthalmology & Visual Sciences,
  • R. J. C. Albuquerque
    University of Kentucky, Lexington, Kentucky
    Ophthalmology & Visual Sciences,
    Physiology,
  • M. E. Kleinman
    University of Kentucky, Lexington, Kentucky
    Ophthalmology & Visual Sciences,
  • S. De Falco
    Institute of Genetics and Biophysics, Consiglio Nazionale delle Ricerche, Naples, Italy
  • T. A. Wilgus
    Center for Wound Healing & Tissue Regeneration, University of Illinois at Chicago College of Dentistry, Chicago, Illinois
  • L. A. DiPietro
    Center for Wound Healing & Tissue Regeneration, University of Illinois at Chicago College of Dentistry, Chicago, Illinois
  • J. Ambati
    University of Kentucky, Lexington, Kentucky
    Ophthalmology & Visual Sciences,
    Physiology,
  • Footnotes
    Commercial Relationships  M. Nozaki, None; R.J.C. Albuquerque, None; M.E. Kleinman, None; S. De Falco, None; T.A. Wilgus, None; L.A. DiPietro, None; J. Ambati, None.
  • Footnotes
    Support  NEI/NIH, Research to Prevent Blindness, Burroughs Wellcome Fund, American Health Assistance Foundation
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 525. doi:https://doi.org/
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      M. Nozaki, R. J. C. Albuquerque, M. E. Kleinman, S. De Falco, T. A. Wilgus, L. A. DiPietro, J. Ambati; Non-Targeted siRNA Suppress Angiogenesis in the Cornea, Dermis and Hind Limb. Invest. Ophthalmol. Vis. Sci. 2008;49(13):525. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Small interfering RNAs (siRNAs) are presumed to specifically knockdown target mRNAs in a sequence-dependent manner. Clinical trials of siRNAs targeting pro-angiogenic VEGF and VEGFR-1 are ongoing. Yet, the contribution of specific RNA interference of siRNAs has not been determined in vivo. We have reported that non-targeted siRNA suppresses laser-induced choroidal neovascularization to the same extent as targeted siRNA (Kleinman et al. ARVO, 2008). This study sought to determine the global potential of non-targeted siRNA to inhibit angiogenesis in different organ systems.

Methods: : Balb/C and C57Bl/6 mice were studied. Non-targeted siRNAs were 21-nt (nucleotides) siRNA-Luc (firefly luciferase) or 7-nt siRNA-Luc. Targeted 21-nt siRNA-Vegfa, siRNA buffer or PBS were used for comparison. The mouse models of suture-induced corneal neovascularization, hind limb ischemia (HLI) and dermal wounding neovascularization (WDV) were studied. The extent of the angiogenic response was assessed by immunochemical techniques.

Results: : 21-nt siRNA-Luc and 21-nt siRNA-Vegfa abolished suture-induced corneal neovascularization (NV), whereas 7-nt siRNA-Luc or the siRNA buffer alone did not. In the HLI model, both 21-nt siRNAs showed significantly reduction in angiogenesis by 30% compare to PBS or 7-nt siRNA (p<0.01). Similarly, in the WDV model, both 21-nt siRNAs decreased the percent dermal CD31 positive area by approximately 50% compared to 7-nt siRNA or PBS alone (p<0.01).

Conclusions: : Our data demonstrated that 21-nt siRNAs, targeted and non-targeted, are capable of equally suppressing angiogenesis in the cornea, dermis and hind limb. These findings suggest that the in vivo anti-angiogenic effects of siRNAs are global, length-dependent and sequence non-specific.

Keywords: neovascularization • vascular endothelial growth factor • cornea: basic science 
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