Abstract
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.
Highlights
Loss of Fragile X Mental Retardation Protein (FMRP) induces alterations of neuronal synapses either in their structure or in their functions (Irwin et al, 2000; Nimchinsky et al, 2001) and leads to the human condition known as the Fragile X Syndrome (FXS)
This is even more interesting since, under physiological conditions, the starting point of cerebral visual system maturation is the retinal light sensoring by Rhodopsin occurring during Eye Opening (EO; Gandhi et al, 2008), which ends up in a massive synaptogenesis in the primary visual cortex (Blue and Parnavelas, 1983; Gandhi et al, 2005)
Our work suggests a critical role of the sensorial peripheral dysfunction in the Fmr1−/y overall phenotype, and provides evidence that altered peripheral perception is a component of the sensory processing defect in FXS conditions
Summary
Loss of Fragile X Mental Retardation Protein (FMRP) induces alterations of neuronal synapses either in their structure or in their functions (Irwin et al, 2000; Nimchinsky et al, 2001) and leads to the human condition known as the Fragile X Syndrome (FXS). Concerning vision, it has been shown that visual signal integration is affected in FXS patients, with alteration of spatiotemporal visual processing, reduction of contrast sensitivity for visual stimuli presented at high temporal frequencies, and visual sensitivity for both static (texture difference) and moving images (Kogan et al, 2008; Farzin et al, 2011) These visual defects are associated with cerebral neuron immaturity (Irwin et al, 2000; Bilousova et al, 2009) especially in the primary visual cortex (Berman et al, 2012). Since adult Fmr1−/y retinas present alterations, we investigated the chronological order of this defect especially before EO by exploring molecular, structural and functional features before EO and in young and adult Fmr1−/y retinas
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