Retinal Phenotyping of a Murine Model of Lafora Disease
Lafora disease (LD) is a progressive neurologic disorder caused by biallelic pathogenic variants in <i>EPM2A</i> or <i>EPM2B</i>, leading to tissue accumulation of polyglucosan aggregates termed Lafora bodies (LBs). This study aimed to characterize the retinal phenotype in &l...
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MDPI AG
2023-03-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/4/854 |
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| author | Ajoy Vincent Kashif Ahmed Rowaida Hussein Zorana Berberovic Anupreet Tumber Xiaochu Zhao Berge A. Minassian |
| author_facet | Ajoy Vincent Kashif Ahmed Rowaida Hussein Zorana Berberovic Anupreet Tumber Xiaochu Zhao Berge A. Minassian |
| author_sort | Ajoy Vincent |
| collection | DOAJ |
| description | Lafora disease (LD) is a progressive neurologic disorder caused by biallelic pathogenic variants in <i>EPM2A</i> or <i>EPM2B</i>, leading to tissue accumulation of polyglucosan aggregates termed Lafora bodies (LBs). This study aimed to characterize the retinal phenotype in <i>Epm2a<sup>−/−</sup></i> mice by examining knockout (KO; <i>Epm2a<sup>−/−</sup></i>) 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<sup>2</sup>, at 10 and 14 months, respectively. This is the first study to characterize the retinal phenotype in an <i>Epm2a<sup>−/−</sup></i> 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. |
| first_indexed | 2024-03-11T04:59:29Z |
| format | Article |
| id | doaj.art-e0532e1f97d74ef298baca79adc18725 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T04:59:29Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-e0532e1f97d74ef298baca79adc187252023-11-17T19:23:27ZengMDPI AGGenes2073-44252023-03-0114485410.3390/genes14040854Retinal Phenotyping of a Murine Model of Lafora DiseaseAjoy Vincent0Kashif Ahmed1Rowaida Hussein2Zorana Berberovic3Anupreet Tumber4Xiaochu Zhao5Berge A. Minassian6Department of Ophthalmology and Vision Sciences, Hospital for Sick Children, Toronto, ON M5G 1X8, CanadaGenetics and Genome Biology, Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaGenetics and Genome Biology, Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaThe Center for Phenogenomics, Toronto, ON M5T 3H7, CanadaDepartment of Ophthalmology and Vision Sciences, Hospital for Sick Children, Toronto, ON M5G 1X8, CanadaGenetics and Genome Biology, Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaDivision of Neurology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USALafora disease (LD) is a progressive neurologic disorder caused by biallelic pathogenic variants in <i>EPM2A</i> or <i>EPM2B</i>, leading to tissue accumulation of polyglucosan aggregates termed Lafora bodies (LBs). This study aimed to characterize the retinal phenotype in <i>Epm2a<sup>−/−</sup></i> mice by examining knockout (KO; <i>Epm2a<sup>−/−</sup></i>) 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<sup>2</sup>, at 10 and 14 months, respectively. This is the first study to characterize the retinal phenotype in an <i>Epm2a<sup>−/−</sup></i> 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.https://www.mdpi.com/2073-4425/14/4/854diseaseLafora body disorderLafora<i>EPM2A</i>electroretinographyoptical coherence tomography |
| spellingShingle | Ajoy Vincent Kashif Ahmed Rowaida Hussein Zorana Berberovic Anupreet Tumber Xiaochu Zhao Berge A. Minassian Retinal Phenotyping of a Murine Model of Lafora Disease Genes disease Lafora body disorder Lafora <i>EPM2A</i> electroretinography optical coherence tomography |
| 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 | disease Lafora body disorder Lafora <i>EPM2A</i> electroretinography optical coherence tomography |
| url | https://www.mdpi.com/2073-4425/14/4/854 |
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