December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
Pattern of Activity of Viral and Housekeeping Gene Using Self-inactivating Lentivirus Vector Delivery into the Mouse Retina
Author Affiliations & Notes
  • C Kostic
    Oculogenetic Unit Jules Gonin Eye Hosp Lausanne Switzerland
  • F Chiodini
    Oculogenetic Unit Jules Gonin Eye Hosp Lausanne Switzerland
  • D Hornfeld
    Oculogenetic Unit Jules Gonin Eye Hosp Lausanne Switzerland
  • M Tekaya
    Oculogenetic Unit Jules Gonin Eye Hosp Lausanne Switzerland
  • P Salmon
    Dept of Genetic and Microbiology University Medical Center (CMU) Geneva Switzerland
  • N Déglon
    The Neurosciences Institute Swiss Federal Institute of Technology (EPFL) Lausanne Switzerland
  • P Aebischer
    The Neurosciences Institute Swiss Federal Institute of Technology (EPFL) Lausanne Switzerland
  • F Munier
    Oculogenetic Unit Jules Gonin Eye Hosp Lausanne Switzerland
  • Y Arsenijevic
    Oculogenetic Unit Jules Gonin Eye Hosp Lausanne Switzerland
  • Footnotes
    Commercial Relationships   C. Kostic, None; F. Chiodini, None; D. Hornfeld, None; M. Tekaya, None; P. Salmon, None; N. Déglon, None; P. Aebischer, None; F. Munier, None; Y. Arsenijevic, None. Grant Identification: Support by gebert Rüeff Foundation
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 4612. doi:
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      C Kostic, F Chiodini, D Hornfeld, M Tekaya, P Salmon, N Déglon, P Aebischer, F Munier, Y Arsenijevic; Pattern of Activity of Viral and Housekeeping Gene Using Self-inactivating Lentivirus Vector Delivery into the Mouse Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4612.

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

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Abstract

Abstract: : Purpose: Retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration have an important incidence in the occidental world. The process impaired in this visual decline is a progressive loss of photoreceptors. No therapy exists so far to cure these diseases and gene transfer appears to be promising to prevent photoreceptor loss. In order to design adequate vectors, we explored the activity of different promoters (cytomegalovirus (CMV), phosphoglycerate kinase (PGK), elongation factor-1 (EFS) and rhodopsin (Rho) promoters) in postnatal and adult mice eyes (n=6 to 18). Methods: Self-inactivating lentivirus preparations were injected intravitreously in DBA/2 mice at 3 to 5 days or 8 weeks postnatal, followed by analysis of each promoter activity 7 days later. Results: Cell transductions were observed over a 3 mm distance. As previously described, the CMV promoter was active in retinal pigmented epithelium cells (RPE), photoreceptors and cells of the inner nuclear layer (INL), but more restricted to RPE cells in adult mice eyes. The PGK promoter expression pattern in newborn injected eyes was principally defined as strong in RPE and weak in some cells of the INL. Injected adult eyes showed a predominant expression in RPE cells. The EFS promoter derived from the elongation factor-1 gene, allows a broad expression in the retina of newborn injected mice. Different cell types expressed the GFP reporter gene, such as glial cells, neurons, RPE and rarely photoreceptors. Finally, as expected, the Rho promoter is specifically expressed in photoreceptors. Conclusion: Thus, our study of CMV and PGK promoters suggest that infection in the developing retina is more favorable for transgene expression. Additionally, in future attempts to slow or rescue photoreceptor degeneration by lentiviral delivery of a secreted survival factor, both CMV and PGK promoters should be appropriate due to their strong expression in RPE cells, which are adjacent to the targeted photoreceptors. The EFS promoter could be useful to target neurons of the INL or ganglionic cells that are damaged in glaucomas, because it drives expression in adjacent glial cells. Finally, the Rho promoter is more suitable for genes necessary to be expressed in the photoreceptors themselves.

Keywords: 419 gene transfer/gene therapy • 554 retina • 567 retinal pigment epithelium 
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