May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Complete Inhibition of Neovascularization by VEGF Trap in a Matrigel CNV Model
Author Affiliations & Notes
  • L. Zhao
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA
  • Y. Liu
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA
  • Y. Li
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA
  • Y. Song
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA
  • A.M. Laties
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA
  • J.S. Rudge
    Regeneron Pharmaceuticals, Inc., Tarrytown, NY
  • S.J. Wiegand
    Regeneron Pharmaceuticals, Inc., Tarrytown, NY
  • R. Wen
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA
  • Footnotes
    Commercial Relationships  L. Zhao, None; Y. Liu, None; Y. Li, None; Y. Song, None; A.M. Laties, None; J.S. Rudge, Regeneron Pharmaceuticals, Inc. E; S.J. Wiegand, Regeneron Pharmaceuticals, Inc. E; R. Wen, None.
  • Footnotes
    Support  NIH Grants EY–012727, EY–015289, and an MTAC Grant from the Foundation Fighting Blindness
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 5300. doi:
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      L. Zhao, Y. Liu, Y. Li, Y. Song, A.M. Laties, J.S. Rudge, S.J. Wiegand, R. Wen; Complete Inhibition of Neovascularization by VEGF Trap in a Matrigel CNV Model . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5300.

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

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Abstract
 
Abstract:
 

Age–related macular degeneration (AMD) is the leading cause of visual disability and blindness in the population 65 years or older in the United States. The majority of the cases of severe vision loss with AMD are due to choroidal neovascularization (CNV) with devastating complications. Although the pathogenesis of CNV is not entirely understood, VEGF is implicated in its development. The present work uses VEGF Trap, a potent soluble VEGF receptor composed of ligand–binding portions of human VEGF receptor–1 (VEGFR–1) and VEGFR–2 fused to the Fc segment of IgG1, to bind and neutralize VEGF in a subretinal Matrigel model of CNV.

 

Sprague–Dawley rats (2.5 months old females) were injected with Matrigel into the subretinal space on the temporal side of both eyes through a 33–gauge needle connected to a 10–µl Hamilton microsyringe. VEGF Trap (12.5 mg/kg) or an equimolar concentration of a control protein (human Fc, 6.25 mg/kg) was injected subcutaneously on day 2 and 6. Animals were sacrificed 10 days post–Matrigel injection, and were perfused with a DiI solution to stain blood vessels. Eyes were harvested and serial sections (100 µm each) covering the entire Matrigel–injected area were cut on a Vibratome and examined by fluorescence microscopy. The maximal width W of CNV network in each section was measured (in µm) and the CNV index was calculated by multiply W by the thickness of the section T (100 µm). The sum of CNV indexes of all the sections was taken as the CNV index of an eye.

 

CNV was detected in every eye in the control group, but was completely absent from all eyes of the VEGF Trap treated group. The CNV index for each group was calculated and is presented in the table below.

 

 

VEGF Trap treatment at 12.5 mg/kg (subcutaneous injection) twice during a 10–day experimental period (days 2 and 6 after Matrigel injection) completely prevented CNV development in the Matrigel model. These findings demonstrate the importance of VEGF in CNV induction and development. They also indicate that the VEGF Trap may have utility in the treatment of CNV.

 

 
Keywords: age-related macular degeneration • choroid: neovascularization 
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