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Michel Roux, Aurélie Philipps, Camille Chapot, Jose Sahel, Alvaro Rendon; Alterations in the mGluR6 signaling complex in the retina of mdx3Cv mice, a model of Duchenne Muscular Disease. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5084.
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© ARVO (1962-2015); The Authors (2016-present)
A majority of Duchenne patients presents a strongly reduced electroretinographic b-wave. This phenotype was initially linked to an altered distribution of Kir4.1 potassium in Müller glial cells, through studies on mdx3Cv mice, which have an abnormal ERG response similar to the one of affected patients. However, mice knocked out for the glial dystrophin isoform (Dp71) have similarly mislocalized Kir4.1 channels but a normal ERG. We have thus re-examined mdx3Cv retinas to look for alternative explanations.
Immunohistochemistry and confocal microscopy were used to look at the localization of various proteins around the photoreceptor / bipolar cell synapse.
In mdx3Cv retina, in addition to the mislocalization of the calcium channel Cav1.1 and the Ca2+-ATPase serca2 reported previously (ARVO 2012 abstract), we found a reduction in the immunostaining for many proteins of the mGluR6 associated complex (mGluR6, RGS11, Gβ5, R9AP) at the tip of ON bipolar cell dendrites (N ≥ 4 animals per immunostaining).
The decrease of mGluR6, RGS11, Gβ5 and R9AP should contribute to reduce the amplitude, and to slow the activation of the ON bipolar cell response, in line with the ERG phenotype of mdx3Cv mice and many Duchenne patients. The contribution of Cav1.1 and serca2 contribution is harder to predict. We are starting to compare expression of these proteins in retinas from mice strains with altered dystrophin expression, showing milder (mdx4Cv) or no ERG deficits (mdx, Dp71-null), to better understand the contribution of each DMD gene product in the retina.
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