June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Evaluation of retinal and optic nerve stress in Wfs1-/- mouse model of Wolfram syndrome
Author Affiliations & Notes
  • Delphine Bonnet Wersinger
    Montpellier Neuroscience Institute, INSERM U1051, Montpellier, France
  • Christian Hamel
    Montpellier Neuroscience Institute, INSERM U1051, Montpellier, France
  • Yukio Tanizawa
    Center for Reparative Medicine Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan
  • Guy Lenaers
    Montpellier Neuroscience Institute, INSERM U1051, Montpellier, France
  • Cecile Delettre
    Montpellier Neuroscience Institute, INSERM U1051, Montpellier, France
  • Footnotes
    Commercial Relationships Delphine Bonnet Wersinger, None; Christian Hamel, None; Yukio Tanizawa, None; Guy Lenaers, None; Cecile Delettre, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5085. doi:
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      Delphine Bonnet Wersinger, Christian Hamel, Yukio Tanizawa, Guy Lenaers, Cecile Delettre; Evaluation of retinal and optic nerve stress in Wfs1-/- mouse model of Wolfram syndrome. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5085.

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

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Purpose: Wolfram syndrome (WS) is a rare automal recessive disease associating diabetes mellitus and optic neuropathy in children, leading to blindness at the age of 20. Visual function and structures were evaluated in Wfs1 gene disrupted mouse (Ishihara et al, 2004). However, even if flash visual evoked potential (VEP) were significantly reduced in mutant Wfs1-/- , retinal ganglion cell layer (RGCL) appeared preserved at 12 month old. Several types of stresses were examined to investigate if Wfs1-/- retinal health was altered, namely glial activation, cytoskeleton phosphorylation, endoplasmic reticulum (ER) stress, and changes in RGC gene expression (Nrn1, Thy1).

Methods: One year old Wfs1-/- and +/+ mice were used in accordance to ARVO Statement of the Use of Animals in Ophthalmic and Visual Research. Real-time PCR measured relative amounts of Gfap, Nrn1 and Thy1 mRNA transcripts in retinal cDNAs. Immunohistochemistry of Gfap, BiP, Neurofilament (NF-H) and phospho NF-H proteins was performed on eye transversal cryosections.

Results: Müller cells and astrocyte activations were not detected in Wfs1-/- mice according to GFAP protein and gene expression stabilities in retinas and optic nerves. Phosphorylation of neurofilament was sparsely detected in samples of both genotypes, excluding significant axonal neurodegeneration. RGC specific axonal damage was not detected, since Nrn1 and Thy1 mRNA transcript relative quantities stay unchanged. Endoplasmic reticulum stress marker BiP was similarly expressed in mutant and in wild-type samples; other ER stress markers will be examined.

Conclusions: Wfs1-/- mouse retina and optic nerves didn’t present so far any evidence of stress, according to glial activation, cytoskeleton phosphorylation and ER stress markers. Specifically RGC gene expression was not significantly altered by the mutation, suggesting disruption of mouse Wfs1 gene is not detrimental for RGC homeostasis. Observed reduction of flash VEP amplitudes may thus account for central visual pathway alteration(s). Reference : Ishihara H et al. Hum. Mol. Genet. 2004

Keywords: 610 nerve fiber layer • 531 ganglion cells • 540 glia  

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