May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) Plays an Important Role in the Development of Ocular Neovascularization (NV)
J. Shen; R. Samul; R.L. Silva; Y. Saishin; H. Liu; S.F. Hackett; R. Aitchison; P. Pavco; P.A. Campochiaro
Author Affiliations & Notes
  • J. Shen
    Ophthalmology, Wilmer Eye Institute–Johns Hopkins University, Baltimore, MD
  • R. Samul
    Ophthalmology, Wilmer Eye Institute–Johns Hopkins University, Baltimore, MD
  • R.L. Silva
    Ophthalmology, Wilmer Eye Institute–Johns Hopkins University, Baltimore, MD
  • Y. Saishin
    Ophthalmology, Wilmer Eye Institute–Johns Hopkins University, Baltimore, MD
  • H. Liu
    Ophthalmology, Wilmer Eye Institute–Johns Hopkins University, Baltimore, MD
  • S.F. Hackett
    Ophthalmology, Wilmer Eye Institute–Johns Hopkins University, Baltimore, MD
  • R. Aitchison
    Sirna Therapeutics, Boulder, CO
  • P. Pavco
    Sirna Therapeutics, Boulder, CO
  • P.A. Campochiaro
    Ophthalmology, Wilmer Eye Institute–Johns Hopkins University, Baltimore, MD
  • Footnotes
    Commercial Relationships  J. Shen, None; R. Samul, None; R.L. Silva, None; Y. Saishin, None; H. Liu, None; S.F. Hackett, None; R. Aitchison, Sirna Therapeutics E; P. Pavco, Sirna Therapeutics E; P.A. Campochiaro, Sirna Therapeutics F, C, R.
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 491. doi:
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      J. Shen, R. Samul, R.L. Silva, Y. Saishin, H. Liu, S.F. Hackett, R. Aitchison, P. Pavco, P.A. Campochiaro; Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) Plays an Important Role in the Development of Ocular Neovascularization (NV) . Invest. Ophthalmol. Vis. Sci. 2004;45(13):491.

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Abstract

Abstract: : Purpose: Small interfering RNAs (siRNAs) are short duplex oligonucleotides that can be designed to target and interfere with a specific gene’s expression. In these studies, we used stabilized siRNAs to test the role of VEGFR1 in models of ocular NV. Methods: Real time RT–PCR was used to assess the effect of intravitreous injection of VEGFR1 siRNA on mRNA levels and NV in the retinas of mice with oxygen–induced ischemic retinopathy (OIR). The effect of intravitreous or periocular injection of VEGFR1 siRNA on development of choroidal NV (CNV) at rupture sites in Bruch’s membrane was also determined. Inverted sequence siRNA with the same chemistry as the VEGFR1 siRNA was used as the control. Results: Mice with OIR (P12) were injected with VEGFR1 siRNA in one eye and control in the other. At P15, retinal VEGFR1 mRNA was decreased ∼50% compared to control eyes (652±308 versus 1320±416 copies of VEGFR1 mRNA/105 copies of cyclophilin A mRNA, paired t–test, P=0.0040). Retinal NV was also decreased by ∼50% (P=0.0190). In the CNV model, two intravitreous injections of 1.5 µg of siRNA resulted in a 57% decrease in average CNV area (VEGFR1 siRNA, 0.0056 mm2; inverted control, 0.0145 mm2; P=0.0202). After daily periocular injections of 1.5 µg of VEGFR1 siRNA, the average area of CNV was reduced by 43% compared to daily administration of control (VEGFR1 siRNA, 0.0053 mm2; inverted control, 0.0088 mm2; P=0.0034). Lower doses (0.5 µg) of siRNA delivered by either route of administration resulted in significantly less CNV compared to injections of PBS. Conclusions: Either intravitreous or periocular injection of VEGFR1 siRNA substantially reduces VEGFR1 mRNA levels and suppresses the development of CNV at rupture sites in Bruch’s membrane. Intravitreous injection of VEGFR1 siRNA also reduces VEGFR1 mRNA levels and NV in the retina of mice with OIR. These data suggest that VEGFR1 plays an important role in the development of ocular neovascularization

Keywords: choroid: neovascularization • gene transfer/gene therapy • retinal neovascularization 
© 2004, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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