May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Functional Genomics Study of the RdCVF-/- Mouse Model
Author Affiliations & Notes
  • T. C. Cronin
    Genetics, Inserm, Paris, France
  • I. Lee-Rivera
    Genetics, Inserm, Paris, France
  • W. Rafflesberg
    IGBMC, Strasbourg, France
  • E. Clerin
    Genetics, Inserm, Paris, France
  • B. Kinzel
    Novartis, Basel, Switzerland
  • O. Poch
    IGBMC, Strasbourg, France
  • J.-A. Sahel
    Genetics, Hôpital Quinze-vingts, Paris, France
  • T. Léveillard
    Genetics, Inserm, Paris, France
  • Footnotes
    Commercial Relationships  T.C. Cronin, None; I. Lee-Rivera, None; W. Rafflesberg, None; E. Clerin, None; B. Kinzel, None; O. Poch, None; J. Sahel, None; T. Léveillard, None.
  • Footnotes
    Support  INSERM, RETNET MRTN-CT-2003-504003
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3058. doi:https://doi.org/
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      T. C. Cronin, I. Lee-Rivera, W. Rafflesberg, E. Clerin, B. Kinzel, O. Poch, J.-A. Sahel, T. Léveillard; Functional Genomics Study of the RdCVF-/- Mouse Model. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3058. doi: https://doi.org/.

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

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Abstract

Purpose: : Rod-derived Cone Viability Factor (RdCVF) is a retina-specific protein identified for its therapeutic potential in supporting cone survival during retinal degeneration. A transgenic RdCVF-knockout mouse model was recently produced and shown not to express either of RdCVF’s isoforms at the RNA and protein levels. In this work we describe a transcriptomic and functional characterisation of the RdCVF-/- mouse.

Methods: : RT-PCR and western blot analysis confirmed the absence of RdCVF gene expression. Automated counting of PNA-labelled cells was used to estimate cone number. Thickness measurements were made of resin-embedded sections. Dark-adapted, photopic and flicker ERGs were conducted to evaluate retinal function. TBARS assay kit was utilised for an estimation of lipid peroxidation products in the retinas. RNA was purified by ultracentrifugation through caesium-chloride gradient and hybridised to Affymetrix gene chips for microarray expression profiling of the KO retinas.

Results: : We demonstrate that the retina is compromised by the absence of RdCVF. The phenotype is further exacerbated in stress-induced conditions (light damage or hyperoxic containment) implying that the factor may be involved in a supportive role during retinal injury and degeneration. Reduced flicker ERGs from the mouse further support the evidence that RdCVF may serve as a potential cone-based therapy. Microarray data on the knockout model shows expression changes for genes involved in injury response and apoptosis, oxido-reductase activity, glucose homeostasis and lipid metabolism.

Conclusions: : A role for RdCVF in cell survival signaling based on redox balance mechanisms is supported by data from the knockout mouse.

Keywords: neuroprotection • gene microarray • oxidation/oxidative or free radical damage 
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