July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Quadruple knockout mice lacking four crucial extracellular matrix molecules display impaired synaptic integrity and visual motion processing
Author Affiliations & Notes
  • Jacqueline Reinhard
    Cell Morphology & Mol. Neurobiology, Ruhr-University Bochum, Bochum, Germany
  • Cornelius Müller-Bühl
    Cell Morphology & Mol. Neurobiology, Ruhr-University Bochum, Bochum, Germany
  • Susanne Wiemann
    Cell Morphology & Mol. Neurobiology, Ruhr-University Bochum, Bochum, Germany
  • Veronika Luft
    Cell Morphology & Mol. Neurobiology, Ruhr-University Bochum, Bochum, Germany
  • Marina Palmhof
    Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, Bochum, Germany
  • Stephanie C Joachim
    Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, Bochum, Germany
  • Andreas Faissner
    Cell Morphology & Mol. Neurobiology, Ruhr-University Bochum, Bochum, Germany
  • Footnotes
    Commercial Relationships   Jacqueline Reinhard, None; Cornelius Müller-Bühl, None; Susanne Wiemann, None; Veronika Luft, None; Marina Palmhof, None; Stephanie Joachim, None; Andreas Faissner, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4439. doi:
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      Jacqueline Reinhard, Cornelius Müller-Bühl, Susanne Wiemann, Veronika Luft, Marina Palmhof, Stephanie C Joachim, Andreas Faissner; Quadruple knockout mice lacking four crucial extracellular matrix molecules display impaired synaptic integrity and visual motion processing. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4439.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Extracellular matrix (ECM) proteins play an important role in synapse formation and plasticity. Nevertheless, the functional importance of the ECM in the retina is still poorly understood. To investigate the relevance of the ECM in retinal function, we analyzed quadruple knockout (KO) mice lacking the four molecules brevican, neurocan, tenascin-C and tenascin-R.

Methods : Electroretinogram (ERG) recordings were performed in adult, 14-16 week old quadruple KO and wildtype (WT) mice of either sex (n=8/group). The optokinetic reflex (OKR), a basic mechanism to stabilize moving objects on the retina, was also analyzed (n=6/group). Immunohistochemical stainings were performed and visualized by confocal laser-scanning microscopy (n=7-8/group). Using anti-choline acetyl-transferase (ChAT), cholinergic direction-selective starburst amacrine cells (SACs) were stained and counted on retinal flat-mounts. The number of inhibitory γ-aminobutyric acid receptor type A (GABA-R) positive cells was counted on retinal sections. Also, immunoreactivity of the excitatory vesicular glutamate transporter 1 (VGlut1) was investigated. For statistical analyses the Student`s t-test or Mann-Whitney U test were used.

Results : ERG recordings revealed significantly reduced a-wave (p<0.05) and b-wave (p<0.001) amplitudes in quadruple KO compared to WT mice. OKR analyses showed a significant reduction in the numbers of saccades in KO animals (p<0.01). A significantly reduced number of SACs could be noted in the ganglion cell layer of KO mice (p=0.01). Additionally, KO mice showed fewer GABA-R+ cells in the ganglion cell layer (WT: 92.5 ± 1.3 cells/mm, KO: 84.5 ± 1.2 cells/mm, p=0.01). Area measurements revealed a significantly increased VGlut1-staining in the inner plexiform (p=0.008) and outer plexiform layer (p=0.0002).

Conclusions : Quadruple KO mice exhibit reduced a- and b-wave amplitudes, suggesting impaired synaptic integrity. Most interestingly, diminished visual motion processing was evident in these mice, which might be caused by the loss of cholinergic direction-selective SACs. Furthermore, our study implies an impaired balance of inhibitory GABAergic and excitatory glutamatergic neurotransmission in the quadruple KO retina. Collectively, our findings indicate that the lack of four ECM proteins leads to severe impairment of synaptic integrity and visual motion processing.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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