May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
A Reproducible and Quantifiable Model of Choroidal Neovascularization Induced by Vegf After Subretinal Adenoviral Gene Transfer in the Rabbit
Author Affiliations & Notes
  • S. Julien
    University Eye Hospital of Tuebingen, Tuebingen, Germany
    Section of Experimental Vitreoretinal Surgery,
  • F. Kreppel
    Division of Gene Therapy, University of Ulm, Ulm, Germany
  • S. Beck
    University Eye Hospital of Tuebingen, Tuebingen, Germany
    Retinal Diagnostics Research Group,
  • P. Heiduschka
    University Eye Hospital of Tuebingen, Tuebingen, Germany
    Section of Experimental Vitreoretinal Surgery,
  • V. Brito
    Division of Gene Therapy, University of Ulm, Ulm, Germany
  • S. Schnichels
    University Eye Hospital of Tuebingen, Tuebingen, Germany
    Section of Experimental Vitreoretinal Surgery,
  • S. Kochanek
    Division of Gene Therapy, University of Ulm, Ulm, Germany
  • U. Schraermeyer
    University Eye Hospital of Tuebingen, Tuebingen, Germany
    Section of Experimental Vitreoretinal Surgery,
  • Footnotes
    Commercial Relationships  S. Julien, None; F. Kreppel, None; S. Beck, None; P. Heiduschka, None; V. Brito, None; S. Schnichels, None; S. Kochanek, None; U. Schraermeyer, None.
  • Footnotes
    Support  DFG SCHR 436/11-2
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 295. doi:https://doi.org/
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      S. Julien, F. Kreppel, S. Beck, P. Heiduschka, V. Brito, S. Schnichels, S. Kochanek, U. Schraermeyer; A Reproducible and Quantifiable Model of Choroidal Neovascularization Induced by Vegf After Subretinal Adenoviral Gene Transfer in the Rabbit. Invest. Ophthalmol. Vis. Sci. 2008;49(13):295. doi: https://doi.org/.

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

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Abstract

Purpose: : To determine the effects of the vascular endothelial growth factor (VEGF)-A165 delivered using a high capacity adenoviral vector (HC Ad.VEGF-A) on vascular growth and pathological changes in the rabbit eye and to combine different detection methods of VEGF-A165 overexpression-induced neovascularization in the rabbit.

Methods: : HC Ad.VEGF-A165 was constructed and injected at 5x106 infectious units into the subretinal space of the rabbit eye. The development of neovascularization and the expression of HC Ad-transduced VEGF-A165 protein were followed up in vivo by scanning laser ophthalmoscopy, and fluorescein and indocyanine green angiographies and ex vivo by electron microscopy and immunohistochemistry four weeks after the injection.

Results: : In the present model, we observed a choroidal neovascularization (CNV) with leakage in 83% of the rabbit eyes. Our findings present clear indications that there is a significant effect on the endothelial cells of the choriocapillaris after the subretinal transduction of the retinal pigment epithelium (RPE) with VEGF-A165 vector. The choroidal endothelial cells are activated, endothel junctions open, the fenestration is minimised, while the endothelial cells augment the extracellular matrix, begin to migrate and infiltrate the Bruch’s membrane at the same time. They also proliferate and form pathological vessels in the subretinal space. Moreover, an increased expression of FGF and VEGF-A accompanied with stimulation of macrophages, retinal oedema and loss of photoreceptors were observed.

Keywords: gene transfer/gene therapy • age-related macular degeneration • vascular endothelial growth factor 
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