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Retinal Phenotyping of a Murine Model of Lafora Disease

Lafora disease (LD) is a progressive neurologic disorder caused by biallelic pathogenic variants in EPM2A or EPM2B, leading to tissue accumulation of polyglucosan aggregates termed Lafora bodies (LBs). This study aimed to characterize the retinal phenotype in Epm2a(−/−) mice by examining knockout (K...

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Autores principales: Vincent, Ajoy, Ahmed, Kashif, Hussein, Rowaida, Berberovic, Zorana, Tumber, Anupreet, Zhao, Xiaochu, Minassian, Berge A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137594/
https://www.ncbi.nlm.nih.gov/pubmed/37107612
http://dx.doi.org/10.3390/genes14040854
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author Vincent, Ajoy
Ahmed, Kashif
Hussein, Rowaida
Berberovic, Zorana
Tumber, Anupreet
Zhao, Xiaochu
Minassian, Berge A.
author_facet Vincent, Ajoy
Ahmed, Kashif
Hussein, Rowaida
Berberovic, Zorana
Tumber, Anupreet
Zhao, Xiaochu
Minassian, Berge A.
author_sort Vincent, Ajoy
collection PubMed
description Lafora disease (LD) is a progressive neurologic disorder caused by biallelic pathogenic variants in EPM2A or EPM2B, leading to tissue accumulation of polyglucosan aggregates termed Lafora bodies (LBs). This study aimed to characterize the retinal phenotype in Epm2a(−/−) mice by examining knockout (KO; Epm2a(−/−)) and control (WT) littermates at two time points (10 and 14 months, respectively). In vivo exams included electroretinogram (ERG) testing, optical coherence tomography (OCT) and retinal photography. Ex vivo retinal testing included Periodic acid Schiff Diastase (PASD) staining, followed by imaging to assess and quantify LB deposition. There was no significant difference in any dark-adapted or light-adapted ERG parameters between KO and WT mice. The total retinal thickness was comparable between the groups and the retinal appearance was normal in both groups. On PASD staining, LBs were observed in KO mice within the inner and outer plexiform layers and in the inner nuclear layer. The average number of LBs within the inner plexiform layer in KO mice were 1743 ± 533 and 2615 ± 915 per mm(2), at 10 and 14 months, respectively. This is the first study to characterize the retinal phenotype in an Epm2a(−/−) mouse model, demonstrating significant LB deposition in the bipolar cell nuclear layer and its synapses. This finding may be used to monitor the efficacy of experimental treatments in mouse models.
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spelling pubmed-101375942023-04-28 Retinal Phenotyping of a Murine Model of Lafora Disease Vincent, Ajoy Ahmed, Kashif Hussein, Rowaida Berberovic, Zorana Tumber, Anupreet Zhao, Xiaochu Minassian, Berge A. Genes (Basel) Communication Lafora disease (LD) is a progressive neurologic disorder caused by biallelic pathogenic variants in EPM2A or EPM2B, leading to tissue accumulation of polyglucosan aggregates termed Lafora bodies (LBs). This study aimed to characterize the retinal phenotype in Epm2a(−/−) mice by examining knockout (KO; Epm2a(−/−)) and control (WT) littermates at two time points (10 and 14 months, respectively). In vivo exams included electroretinogram (ERG) testing, optical coherence tomography (OCT) and retinal photography. Ex vivo retinal testing included Periodic acid Schiff Diastase (PASD) staining, followed by imaging to assess and quantify LB deposition. There was no significant difference in any dark-adapted or light-adapted ERG parameters between KO and WT mice. The total retinal thickness was comparable between the groups and the retinal appearance was normal in both groups. On PASD staining, LBs were observed in KO mice within the inner and outer plexiform layers and in the inner nuclear layer. The average number of LBs within the inner plexiform layer in KO mice were 1743 ± 533 and 2615 ± 915 per mm(2), at 10 and 14 months, respectively. This is the first study to characterize the retinal phenotype in an Epm2a(−/−) mouse model, demonstrating significant LB deposition in the bipolar cell nuclear layer and its synapses. This finding may be used to monitor the efficacy of experimental treatments in mouse models. MDPI 2023-03-31 /pmc/articles/PMC10137594/ /pubmed/37107612 http://dx.doi.org/10.3390/genes14040854 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Vincent, Ajoy
Ahmed, Kashif
Hussein, Rowaida
Berberovic, Zorana
Tumber, Anupreet
Zhao, Xiaochu
Minassian, Berge A.
Retinal Phenotyping of a Murine Model of Lafora Disease
title Retinal Phenotyping of a Murine Model of Lafora Disease
title_full Retinal Phenotyping of a Murine Model of Lafora Disease
title_fullStr Retinal Phenotyping of a Murine Model of Lafora Disease
title_full_unstemmed Retinal Phenotyping of a Murine Model of Lafora Disease
title_short Retinal Phenotyping of a Murine Model of Lafora Disease
title_sort retinal phenotyping of a murine model of lafora disease
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137594/
https://www.ncbi.nlm.nih.gov/pubmed/37107612
http://dx.doi.org/10.3390/genes14040854
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