May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Gene Transfer of Retinal Ganglion Cells (RGCs) by High-Capacity Adenovirus (HC-Ad) Vector Expressing Pigment Epithelium-Derived Factor (PEDF) Protects them Against Neurodegeneration in vivo
Author Affiliations & Notes
  • I. Semkova
    Center for Molecular Medicine Cologne (ZMMK), University of Cologne, Cologne, Germany
  • J. Jordan
    Department of Vitreo-Retinal Surgery, University of Cologne, Cologne, Germany
  • F. Kreppel
    Department of Vitreo-Retinal Surgery, University of Cologne, Cologne, Germany
  • S. Kochanek
    Department of Vitreo-Retinal Surgery, University of Cologne, Cologne, Germany
  • U. Schraermeyer
    Department of Vitreo-Retinal Surgery, University of Cologne, Cologne, Germany
  • Footnotes
    Commercial Relationships  I. Semkova, None; J. Jordan, None; F. Kreppel, None; S. Kochanek, CEVEC I; U. Schraermeyer, CEVEC I.
  • Footnotes
    Support  DFG SCHR436/11-1, Ilse-Palm Stiftung, and Retinovit Foundation
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 148. doi:
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    • Get Citation

      I. Semkova, J. Jordan, F. Kreppel, S. Kochanek, U. Schraermeyer; Gene Transfer of Retinal Ganglion Cells (RGCs) by High-Capacity Adenovirus (HC-Ad) Vector Expressing Pigment Epithelium-Derived Factor (PEDF) Protects them Against Neurodegeneration in vivo . Invest. Ophthalmol. Vis. Sci. 2003;44(13):148.

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

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Abstract

Abstract: : Purpose:Degeneration of RGCs due to traumatic and ischemic insults and glaucoma leads to a permanent loss of the vision. Gene transfer offers a promising strategy for a delivery of therapeutic proteins into the eye that can increase the survival of RGCs and the regeneration of lesioned RGC axons. HC-Ad vectors have low toxicity and immunogenicity that allow a stable transgene expression for a long period. In a rat model of axonal crush-induced degeneration of RGCs we investigated the capacity of genetically induced PEDF to protect retinal neurons against damage. Methods:Long Evans rats were used. The RGCs were labeled via stereotactical injection of neurotracer Fluorogold into the intact axon terminals in superior colliculs. Three days later, the optic nerve was exposed and a reproducible crush injury was induced by pre-calibrated cross-acting forceps for 30 seconds. Immediatelly after that, the animals received a single intravitreal injection of HC-Ad vector expressing PEDF (HC-Ad.PEDF) (1 x 107 infectiuos particles)and HC-Ad vector expressing enhanced green fluorescence protein (EGFP) (HC-Ad.EGFP) (2 x 106 infectious particles) as a control in a volume of 1 µl/eye. Ten days later, the survival of RGCs was investigated by counting the number of Fluorogold labeled cells on retinal flatmounts. In another set of experiments, the intact axon terminals in superior colliculi were stereotactically injected with HC-Ad.EGFP (2 x 106 infectious particles) in a volume of 5 µl. Ten days later, the expression of transgene in RGCs was investigated on retinal flatmounts. Results:Significantly greater numbers of RGCs survived in the retinas exposed to HC-Ad.PEDF vector than in the retinas exposed to HC-Ad.EGFP or vehicle. In all experimental groups no signs of inflammation or toxic effects were observed. Furthermore, EGFP expression was observed in RGCs of the contralateral eye 10 days after injection of HC-Ad.EGFP vector into the superior colliculus. Conclusions:We demonstrate that a single intravitreal injection of HC-Ad.PEDF vector rescues injured RGCs in a rat model of optical nerve crush injury. Furthermore, RGCs were targeted by retrograde transport of HC-Ad.EGFP vector after application to the superior colliculus that offers another way for specific transduction of RGCs with therapeutic genes.

Keywords: gene transfer/gene therapy • animal model • neuroprotection 
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