May 2008
Volume 49, Issue 13
ARVO Annual Meeting Abstract  |   May 2008
Retinal Crystallins Are Downregulated in Scn8a (Nav1.6)-Null Mice
Author Affiliations & Notes
  • L. W. Chu
    Biology, Dalhousie University, Halifax, Nova Scotia, Canada
  • A. J. Mears
    Ophthalmology, Ottawa Health Research Institute and University of Ottawa, Ottawa, Ontario, Canada
  • P. D. Cote
    Biology, Dalhousie University, Halifax, Nova Scotia, Canada
  • Footnotes
    Commercial Relationships  L.W. Chu, None; A.J. Mears, None; P.D. Cote, None.
  • Footnotes
    Support  NSERC
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3093. doi:
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      L. W. Chu, A. J. Mears, P. D. Cote; Retinal Crystallins Are Downregulated in Scn8a (Nav1.6)-Null Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3093. doi:

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

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Purpose: : Mice harboring 'null' mutations in the voltage-gated sodium channel alpha subunit gene Scn8a (gene product Nav1.6) produce abnormal electroretinograms with reduced a- and b-wave amplitude but have a normal retinal histology. Our goal is to establish the Scn8a-dependent pathways through the identification of differentially expressed genes in Scn8a-deficient retinas vs. normal retinas.

Methods: : The expression of Scn8a-regulated genes and how they affect the developing retina will be examined through the use of the MEEBO 38.5K DNA chip (Microarrays Inc). Candidate genes of interest revealed will be further analyzed and verified using immunocytochemistry and in situ hybridization.

Results: : Initial experiments have revealed that in Scn8a-null mice a number of genes belonging to the crystallin family are significantly downregulated. While the alpha-crystallins have been found to be important for maintaining the integrity of the cytoskeleton and prevent apoptosis both in vitro and in vivo, recent experiments suggest that the expression of beta/gamma-crystallins in the retina function as stress proteins. Additionally, glial fibrillary acidic protein (GFAP) is observed to be significantly upregulated four-fold in Scn8a-null mice. Found in retinal astrocytes, GFAP is an established indicator of retinal stress; its expression in retinal astrocytes and Muller cells has been demonstrated to be modulated by cytokines and retinal pathology, including age related macular degeneration (AMD).

Conclusions: : Simultaneous downregulation of many members of the same gene family suggests that a pathway is shared through the interaction of common regulatory elements and these elements may be regulated by Scn8a-mediated sodium currents.

Keywords: retinal development • ion channels • crystallins 

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