Cellular localization of the FMRP in rat retina

Abstract

The fragile X mental retardation protein (FMRP) is a regulator of local translation through its mRNA targets in the neurons. Previous studies have demonstrated that FMRP may function in distinct ways during the development of different visual subcircuits. However, the localization of the FMRP in different types of retinal cells is unclear. In this work, the FMRP expression in rat retina was detected by Western blot and immunofluorescence double labeling. Results showed that the FMRP expression could be detected in rat retina and that the FMRP had a strong immunoreaction (IR) in the ganglion cell (GC) layer, inner nucleus layer (INL), and outer plexiform layer (OPL) of rat retina. In the outer retina, the bipolar cells (BCs) labeled by homeobox protein ChX10 (ChX10) and the horizontal cells (HCs) labeled by calbindin (CB) were FMRP-positive. In the inner retina, GABAergic amacrine cells (ACs) labeled by glutamate decarbonylase colocalized with the FMRP. The dopaminergic ACs (tyrosine hydroxylase marker) and cholinergic ACs (choline acetyltransferase (ChAT) marker) were co-labeled with the FMRP. In most GCs (labeled by Brn3a) and melanopsin-positive intrinsically photosensitive retinal GCs (ipRGCs) were also FMRP-positive. The FMRP expression was observed in the cellular retinal binding protein-positive Müller cells. These results suggest that the FMRP could be involved in the visual pathway transmission.

Electroretinography and contrast sensitivity, complementary translational biomarkers of sensory deficits in the visual system of individuals with fragile X syndrome

“…These impairments may be due to the synaptic immaturity observed in post-mortem labeling in the visual cortex [31]. Retinal neurons share the same neuroectodermal embryonic origins with cortical neurons [32,33], and both neuron types express FMRP [34][35][36][37]. The retinal neural network shares similarities with other neural networks of the brain, in terms of connectivity [38,39], but the retina's accessibility allows for specific retinal signaling pathways to be probed and measured noninvasively with electroretinography (ERG).…”

Expression of SH3 and Multiple Ankyrin Repeat Domains Protein 3 in Mouse Retina

“…Using double-labeling experiments, we further explored the co-expression pattern of SHANK3 and the different subtypes of ACs. GABAergic ACs, which account for a majority of ACs in the mammalian retina, are all large-field ACs labeled by GAD 65 (Halbedl et al, 2016;Zhang et al, 2020). As shown in Figure 4a', the somata of the GAD65-positive GABAergic ACs are located in the inner part of the INL and their processes are widely expressed in the IPL.…”

“…The retinas were prepared as previously described in detail (Zhang et al, 2020) with minor modifications. The mice were deeply anesthetized via 20% Urethane and transcardially perfused with saline followed by 4% paraformaldehyde (both ice-cold).…”

FMR protein: Evidence of an emerging role in retinal aging?

“…In addition, few studies focusing on Dark-Adapted (DA) conditions have also shown alteration in the b-wave amplitude (Constable et al, 2016). In parallel of these clinical works, preclinical data demonstrated that FMRP is expressed in all retinal layers (Rossignol et al, 2014;Guimaraes-Souza et al, 2016;Zhang et al, 2020) and that its total absence in young and adult Fmr1 KO mice (murine model of FXS) is associated to several protein deficits, neuronal immaturity, and thus to retinal functional alterations (Rossignol et al, 2014;Perche et al, 2018) as observed in human conditions (Perche et al, 2021). Moreover, retinal Fmrp content is dependent of light exposure, since studies showed higher levels of Fmrp RNA in retinas exposed to light when compared to DA retinas (Guimaraes-Souza et al, 2016).…”