May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Effect of SU1498, an Inhibitor of Vascular Endothelial Growth Factor Receptor-2, in a Transgenic Murine Model of Retinoblastoma
Author Affiliations & Notes
  • C. M. Cebulla
    Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida
  • M. E. Jockovich
    Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida
  • H. Boutrid
    Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida
  • Y. Piña
    Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida
  • M. Ruggeri
    Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida
  • S. Jiao
    Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida
  • S. K. Bhattacharya
    Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida
  • W. J. Feuer
    Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida
  • T. G. Murray
    Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida
  • Footnotes
    Commercial Relationships  C.M. Cebulla, None; M.E. Jockovich, None; H. Boutrid, None; Y. Piña, None; M. Ruggeri, None; S. Jiao, None; S.K. Bhattacharya, None; W.J. Feuer, None; T.G. Murray, None.
  • Footnotes
    Support  NIH Grant RO1 EY013629, NIH Grant P30-EY014801, Research to Prevent Blindness
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 23. doi:https://doi.org/
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      C. M. Cebulla, M. E. Jockovich, H. Boutrid, Y. Piña, M. Ruggeri, S. Jiao, S. K. Bhattacharya, W. J. Feuer, T. G. Murray; Effect of SU1498, an Inhibitor of Vascular Endothelial Growth Factor Receptor-2, in a Transgenic Murine Model of Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):23. doi: https://doi.org/.

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

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Abstract

Purpose: : SU1498, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), inhibits retinal neovascular diseases. To determine if this drug might have clinical utility against retinoblastoma, we evaluated the effects of SU1498, as well as the expression of VEGFR-2, in a transgenic animal model of retinoblastoma. Optical coherence tomography (OCT) was evaluated as a technology to measure retinal tumors in vivo, in response to treatment.

Methods: : This study was approved by the IACUC and follows ARVO guidelines. Immunofluorescence analysis was performed to evaluate the distribution and expression of VEGFR-2 in enucleated eyes from LHβTag transgenic mice and controls at 4, 8, and 12, and 16 weeks of age. VEGFR-2 and phosphorylated (p)VEGFR-2 levels were quantitated by Western blot. OCT was used to pair 10-week-old animals based on tumor volume (n=10), and these animals were treated with 6 periocular injections of SU1498 (50mg/kg, given twice weekly) or vehicle for 3 weeks. Tumor burden was determined by histology and in vivo imaging by OCT.

Results: : VEGFR-2 and pVEGFR-2 expression levels were strongly upregulated during tumorigenesis. However, SU1498 did not significantly reduce tumor burden compared to vehicle (p=0.29). OCT imaging of one matched pair demonstrated equivalent, linear tumor growth despite treatment with SU1498.

Conclusions: : Retinal tumors can be followed non-invasively and quantitatively measured with OCT. VEGFR-2 is strongly upregulated during tumorigenesis in transgenic retinoblastoma; however, SU1498 does not significantly decrease tumor volume in transgenic murine RB.

Keywords: retinoblastoma • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • vascular endothelial growth factor 
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