Frontiers in Cellular Neuroscience (Apr 2018)

Early Retinal Defects in Fmr1−/y Mice: Toward a Critical Role of Visual Dys-Sensitivity in the Fragile X Syndrome Phenotype?

  • Olivier Perche,
  • Olivier Perche,
  • Olivier Perche,
  • Chloé Felgerolle,
  • Chloé Felgerolle,
  • Maryvonne Ardourel,
  • Maryvonne Ardourel,
  • Audrey Bazinet,
  • Audrey Bazinet,
  • Arnaud Pâris,
  • Arnaud Pâris,
  • Rafaëlle Rossignol,
  • Rafaëlle Rossignol,
  • Géraldine Meyer-Dilhet,
  • Géraldine Meyer-Dilhet,
  • Anne-Laure Mausset-Bonnefont,
  • Betty Hébert,
  • Betty Hébert,
  • David Laurenceau,
  • Céline Montécot-Dubourg,
  • Céline Montécot-Dubourg,
  • Arnaud Menuet,
  • Arnaud Menuet,
  • Jean-Charles Bizot,
  • Jacques Pichon,
  • Jacques Pichon,
  • Isabelle Ranchon-Cole,
  • Sylvain Briault,
  • Sylvain Briault,
  • Sylvain Briault

DOI
https://doi.org/10.3389/fncel.2018.00096
Journal volume & issue
Vol. 12

Abstract

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Fragile X Syndrome (FXS) is caused by a deficiency in Fragile X Mental Retardation Protein (FMRP) leading to global sensorial abnormalities, among which visual defects represent a critical part. These visual defects are associated with cerebral neuron immaturity especially in the primary visual cortex. However, we recently demonstrated that retinas of adult Fmr1−/y mice, the FXS murine model, present molecular, cellular and functional alterations. However, no data are currently available on the evolution pattern of such defects. As retinal stimulation through Eye Opening (EO) is a crucial signal for the cerebral visual system maturation, we questioned the precocity of molecular and functional retinal phenotype. To answer this question, we studied the retinal molecular phenotype of Fmr1−/y mice before EO until adult age and the consequences of the retinal loss of Fmrp on retinal function in young and adult mice. We showed that retinal molecular defects are present before EO and remain stable at adult age, leading to electrophysiological impairments without any underlying structural changes. We underlined that loss of Fmrp leads to a wide range of defects in the retina, settled even before EO. Our work demonstrates a critical role of the sensorial dysfunction in the Fmr1−/y mice overall phenotype, and provides evidence that altered peripheral perception is a component of the sensory processing defect in FXS conditions.

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