Cargando…

ERG Responses in Mice with Deletion of the Synaptic Ribbon Component RIBEYE

PURPOSE: To determine the influence of RIBEYE deletion and the resulting absence of synaptic ribbons on retinal light signaling by electroretinography. METHODS: Full-field flash electroretinograms (ERGs) were recorded in RIBEYE knock-out (KO) and wild-type (WT) littermate mice under photopic and sco...

Descripción completa

Detalles Bibliográficos
Autores principales: Fairless, Richard, Williams, Sarah K., Katiyar, Rashmi, Maxeiner, Stephan, Schmitz, Frank, Diem, Ricarda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405791/
https://www.ncbi.nlm.nih.gov/pubmed/32437548
http://dx.doi.org/10.1167/iovs.61.5.37
_version_ 1783567319927095296
author Fairless, Richard
Williams, Sarah K.
Katiyar, Rashmi
Maxeiner, Stephan
Schmitz, Frank
Diem, Ricarda
author_facet Fairless, Richard
Williams, Sarah K.
Katiyar, Rashmi
Maxeiner, Stephan
Schmitz, Frank
Diem, Ricarda
author_sort Fairless, Richard
collection PubMed
description PURPOSE: To determine the influence of RIBEYE deletion and the resulting absence of synaptic ribbons on retinal light signaling by electroretinography. METHODS: Full-field flash electroretinograms (ERGs) were recorded in RIBEYE knock-out (KO) and wild-type (WT) littermate mice under photopic and scotopic conditions, with oscillatory potentials (OPs) extracted by digital filtering. Flicker ERGs and ERGs following intravitreal injection of pharmacological agents were also obtained under scotopic conditions. RESULTS: The a-wave amplitudes were unchanged between RIBEYE KO and WT mice; however, the b-wave amplitudes were reduced in KOs under scotopic, but not photopic, conditions. Increasing stimulation frequency led to a greater reduction in RIBEYE KO b-wave amplitudes compared with WTs. Furthermore, we observed prominent, supernormal OPs in RIBEYE KO mice in comparison with WT mice. Following intravitreal injections with l-2 amino-4-phosphonobutyric acid and cis-2,3 piperidine dicarboxylic acid to block ON and OFF responses at photoreceptor synapses, OPs were completely abolished in both mice types, indicating a synaptic origin of the prominent OPs in the KOs. Conversely, tetrodotoxin treatment to block voltage-gated Na(+) channels/spiking neurons did not differentially affect OPs in WT and KO mice. CONCLUSIONS: The decreased scotopic b-wave and decreased responses to increased stimulation frequencies are consistent with signaling malfunctions at photoreceptor and inner retinal ribbon synapses. Because phototransduction in the photoreceptor outer segments is unaffected in the KOs, their supernormal OPs presumably result from a dysfunction in retinal synapses. The relatively mild ERG phenotype in KO mice, particularly in the photopic range, is probably caused by compensatory mechanisms in retinal signaling pathways.
format Online
Article
Text
id pubmed-7405791
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher The Association for Research in Vision and Ophthalmology
record_format MEDLINE/PubMed
spelling pubmed-74057912020-08-19 ERG Responses in Mice with Deletion of the Synaptic Ribbon Component RIBEYE Fairless, Richard Williams, Sarah K. Katiyar, Rashmi Maxeiner, Stephan Schmitz, Frank Diem, Ricarda Invest Ophthalmol Vis Sci Visual Neuroscience PURPOSE: To determine the influence of RIBEYE deletion and the resulting absence of synaptic ribbons on retinal light signaling by electroretinography. METHODS: Full-field flash electroretinograms (ERGs) were recorded in RIBEYE knock-out (KO) and wild-type (WT) littermate mice under photopic and scotopic conditions, with oscillatory potentials (OPs) extracted by digital filtering. Flicker ERGs and ERGs following intravitreal injection of pharmacological agents were also obtained under scotopic conditions. RESULTS: The a-wave amplitudes were unchanged between RIBEYE KO and WT mice; however, the b-wave amplitudes were reduced in KOs under scotopic, but not photopic, conditions. Increasing stimulation frequency led to a greater reduction in RIBEYE KO b-wave amplitudes compared with WTs. Furthermore, we observed prominent, supernormal OPs in RIBEYE KO mice in comparison with WT mice. Following intravitreal injections with l-2 amino-4-phosphonobutyric acid and cis-2,3 piperidine dicarboxylic acid to block ON and OFF responses at photoreceptor synapses, OPs were completely abolished in both mice types, indicating a synaptic origin of the prominent OPs in the KOs. Conversely, tetrodotoxin treatment to block voltage-gated Na(+) channels/spiking neurons did not differentially affect OPs in WT and KO mice. CONCLUSIONS: The decreased scotopic b-wave and decreased responses to increased stimulation frequencies are consistent with signaling malfunctions at photoreceptor and inner retinal ribbon synapses. Because phototransduction in the photoreceptor outer segments is unaffected in the KOs, their supernormal OPs presumably result from a dysfunction in retinal synapses. The relatively mild ERG phenotype in KO mice, particularly in the photopic range, is probably caused by compensatory mechanisms in retinal signaling pathways. The Association for Research in Vision and Ophthalmology 2020-05-21 /pmc/articles/PMC7405791/ /pubmed/32437548 http://dx.doi.org/10.1167/iovs.61.5.37 Text en Copyright 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Visual Neuroscience
Fairless, Richard
Williams, Sarah K.
Katiyar, Rashmi
Maxeiner, Stephan
Schmitz, Frank
Diem, Ricarda
ERG Responses in Mice with Deletion of the Synaptic Ribbon Component RIBEYE
title ERG Responses in Mice with Deletion of the Synaptic Ribbon Component RIBEYE
title_full ERG Responses in Mice with Deletion of the Synaptic Ribbon Component RIBEYE
title_fullStr ERG Responses in Mice with Deletion of the Synaptic Ribbon Component RIBEYE
title_full_unstemmed ERG Responses in Mice with Deletion of the Synaptic Ribbon Component RIBEYE
title_short ERG Responses in Mice with Deletion of the Synaptic Ribbon Component RIBEYE
title_sort erg responses in mice with deletion of the synaptic ribbon component ribeye
topic Visual Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405791/
https://www.ncbi.nlm.nih.gov/pubmed/32437548
http://dx.doi.org/10.1167/iovs.61.5.37
work_keys_str_mv AT fairlessrichard ergresponsesinmicewithdeletionofthesynapticribboncomponentribeye
AT williamssarahk ergresponsesinmicewithdeletionofthesynapticribboncomponentribeye
AT katiyarrashmi ergresponsesinmicewithdeletionofthesynapticribboncomponentribeye
AT maxeinerstephan ergresponsesinmicewithdeletionofthesynapticribboncomponentribeye
AT schmitzfrank ergresponsesinmicewithdeletionofthesynapticribboncomponentribeye
AT diemricarda ergresponsesinmicewithdeletionofthesynapticribboncomponentribeye