April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Bax-Induced Apoptosis in Leber’s Congenital Amaurosis: A Dual Role in Rod and Cone Degeneration
Author Affiliations & Notes
  • S. Cottet
    IRO - Inst. for Res. in Ophthalmology, Sion, Valais, Switzerland
  • S. Métrailler
    IRO - Inst. for Res. in Ophthalmology, Sion, Valais, Switzerland
  • S. Hamann
    IRO - Inst. for Res. in Ophthalmology, Sion, Valais, Switzerland
  • D. F. Schorderet
    IRO - Inst. for Res. in Ophthalmology, Sion, Valais, Switzerland
    EPFL - Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
  • Footnotes
    Commercial Relationships  S. Cottet, None; S. Métrailler, None; S. Hamann, None; D.F. Schorderet, None.
  • Footnotes
    Support  FNRS Grant 3100A0-118336
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4462. doi:
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      S. Cottet, S. Métrailler, S. Hamann, D. F. Schorderet; Bax-Induced Apoptosis in Leber’s Congenital Amaurosis: A Dual Role in Rod and Cone Degeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4462.

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

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Abstract

Purpose: : We previously observed that anti- and pro-apoptotic genes of the Bcl-2 family were differentially expressed during the development of LCA in the Rpe65-/- mouse model (Cottet et al. 2006). Moreover, we reported that activation and translocation of pro-apoptotic Bax to the mitochondria was associated with apoptosis of rod photoreceptors as the disease progressed (Cottet et al. 2008). In this study we challenged whether disruption of the pro-apoptotic pro-apoptotic Bax protein is sufficient to protect photoreceptor cells against apoptosis.

Methods: : Apoptosis of photoreceptor cells was addressed by TUNEL assay on flatmounted retinas. Counting of the rod nuclei within the ONL was performed following hematoxylin/eosin histological staining of retina sections. Expression level and localization of photoreceptor gene markers were assessed by quantitative PCR and immunohistological analyses.

Results: : While expression of rod photoreceptor genes was decreased in Rpe65-deficient retina, expression level remained unchanged in Rpe65-/- / Bax-/- mice. Moreover, OS dysorganization and shortening as well as decrease in ONL thickness observed in diseased retina were prevented in mice lacking functional Bax protein. TUNEL assay confirmed that Bax-dependent rod photoreceptor apoptosis was abolished in Rpe65-/- / Bax-/- mice. However, early and fast degeneration of cone cells was not prevented in Rpe65-/- / Bax-/- mice, indicating that Bax-induced apoptotic pathway was not involved in the degenerating process of cones in Rpe65-deficient retina.

Conclusions: : Altogether, these data show for the first time that a single genetic mutation can trigger two independent apoptotic pathways in rod and cone photoreceptors in LCA disease. While pro-apoptotic Bax is essential to trigger rod photoreceptor apoptosis, early degeneration of cones is not dependent on Bax-mediated apoptotic pathway in Rpe65-deficientmice.

Keywords: photoreceptors • retinal degenerations: cell biology • apoptosis/cell death 
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