May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
EIAV Vector Delivery of Angiostatin or Endostatin Inhibits Angiogenesis and Vascular Hyperpermeability in Experimental CNV
Author Affiliations & Notes
  • K.S. Balaggan
    Molecular Therapy, Institute Ophthalmology, London, United Kingdom
  • K. Binley
    Biological Systems Group, Oxford BioMedica (UK) Ltd, Oxford, United Kingdom
  • M. Esapa
    Biological Systems Group, Oxford BioMedica (UK) Ltd, Oxford, United Kingdom
  • S. Iqball
    Biological Systems Group, Oxford BioMedica (UK) Ltd, Oxford, United Kingdom
  • J. Bainbridge
    Molecular Therapy, Institute Ophthalmology, London, United Kingdom
  • O. Kan
    Biological Systems Group, Oxford BioMedica (UK) Ltd, Oxford, United Kingdom
  • S. Naylor
    Biological Systems Group, Oxford BioMedica (UK) Ltd, Oxford, United Kingdom
  • R.R. Ali
    Molecular Therapy, Institute Ophthalmology, London, United Kingdom
  • Footnotes
    Commercial Relationships  K.S. Balaggan, None; K. Binley, Oxford BioMedica (UK) Ltd E; M. Esapa, Oxford BioMedica (UK) Ltd E; S. Iqball, Oxford BioMedica (UK) Ltd E; J. Bainbridge, None; O. Kan, Oxford BioMedica (UK) Ltd E; S. Naylor, Oxford BioMedica (UK) Ltd E; R.R. Ali, Oxford Biomedica PLC F, C.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 4694. doi:
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      K.S. Balaggan, K. Binley, M. Esapa, S. Iqball, J. Bainbridge, O. Kan, S. Naylor, R.R. Ali; EIAV Vector Delivery of Angiostatin or Endostatin Inhibits Angiogenesis and Vascular Hyperpermeability in Experimental CNV . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4694.

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

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Abstract

Abstract: : Purpose: Developing an effective sustained therapy for CNV remains the key challenge in reducing the severe visual loss in AMD. Successful molecular treatments for CNV are likely to require repeated or sustained delivery of therapeutic agents. Gene therapy strategies can now produce long term expression of transgenes in the eye. Angiostatin and endostatin are potent endogenous angiostatic cytokines. We evaluated the efficacy of a highly expressing minimal non–primate lentiviral vector encoding angiostatin or endostatin in inhibiting angiogenesis and vascular hyperpermeability in a laser–induced model of CNV. Methods: Equine infectious anaemia virus (EIAV) vectors encoding either angiostatin (EIAV.angiostatin) or endostatin (EIAV.endostatin) were injected subretinally into the right eyes of adult mice. Additional mice were injected with a null vector (EIAV.null). The left eyes in all groups served as unprocedured controls. A diode laser was used to focally rupture Bruch’s membrane in all eyes 2 weeks after vector delivery. Early and late phase fluorescein angiography was performed 2 weeks later. CNV areas and fluorescein leakage in vivo from the CNV were quantified in each group. Results:EIAV.endostatin administration produced a 59.5% (p<0.001) reduction in CNV area and a 25.6% (p<0.05) reduction in fluorescein leakage as compared with EIAV.null injected eyes. EIAV.angiostatin produced a 50.0% (p<0.05) reduction in area and a 23.9% (p<0.05) reduction in leakage as compared with the EIAV.null group. EIAV.null did not show any angiostatic or anti–permeability efficacy as compared with unprocedured eyes. Histological and retinal flatmount analysis did not reveal any long–term deleterious effects on mature retinal vasculature. Conclusions: We have demonstrated that a minimal EIAV based vector encoding angiostatic genes can effectively control aberrant angiogenesis and hyperpermeability in a model of CNV without long term deleterious effects on normal retinal vasculature. Similar improvements in these parameters in patients using this technology may translate into a significant and sustained improvement in visual acuity.

Keywords: gene transfer/gene therapy • choroid: neovascularization • age-related macular degeneration 
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