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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. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
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).
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.
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.
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
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