<i>Tlr2</i> Gene Deletion Delays Retinal Degeneration in Two Genetically Distinct Mouse Models of Retinitis Pigmentosa
Although considered a rare retinal dystrophy, retinitis pigmentosa (RP) is the primary cause of hereditary blindness. Given its diverse genetic etiology (>3000 mutations in >60 genes), there is an urgent need for novel treatments that target common features of the disease. TLR2 is a key activa...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/15/7815 |
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| author | Alonso Sánchez-Cruz Andrea C. Méndez Ignacio Lizasoain Pedro de la Villa Enrique J. de la Rosa Catalina Hernández-Sánchez |
| author_facet | Alonso Sánchez-Cruz Andrea C. Méndez Ignacio Lizasoain Pedro de la Villa Enrique J. de la Rosa Catalina Hernández-Sánchez |
| author_sort | Alonso Sánchez-Cruz |
| collection | DOAJ |
| description | Although considered a rare retinal dystrophy, retinitis pigmentosa (RP) is the primary cause of hereditary blindness. Given its diverse genetic etiology (>3000 mutations in >60 genes), there is an urgent need for novel treatments that target common features of the disease. TLR2 is a key activator of innate immune response. To examine its role in RP progression we characterized the expression profile of <i>Tlr2</i> and its adaptor molecules and the consequences of <i>Tlr2</i> deletion in two genetically distinct models of RP: <i>Pde6b<sup>rd10/rd10</sup></i> (<i>rd10</i>) and <i>Rho<sup>P23H/+</sup></i> (<i>P23H/+</i>) mice. In both models, expression levels of <i>Tlr2</i> and its adaptor molecules increased in parallel with those of the proinflammatory cytokine <i>Il1b</i>. In <i>rd10</i> mice, deletion of a single <i>Tlr2</i> allele had no effect on visual function, as evaluated by electroretinography. However, in both RP models, complete elimination of <i>Tlr2</i> attenuated the loss of visual function and mitigated the loss of photoreceptor cell numbers. In <i>Tlr2</i> null <i>rd10</i> mice, we observed decreases in the total number of microglial cells, assessed by flow cytometry, and in the number of microglia infiltrating the photoreceptor layers. Together, these results point to TLR2 as a mutation-independent therapeutic target for RP. |
| first_indexed | 2024-03-10T09:15:39Z |
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| id | doaj.art-21a4e7c6937c41b98536a703f78b1cc6 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:15:39Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-21a4e7c6937c41b98536a703f78b1cc62023-11-22T05:38:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012215781510.3390/ijms22157815<i>Tlr2</i> Gene Deletion Delays Retinal Degeneration in Two Genetically Distinct Mouse Models of Retinitis PigmentosaAlonso Sánchez-Cruz0Andrea C. Méndez1Ignacio Lizasoain2Pedro de la Villa3Enrique J. de la Rosa4Catalina Hernández-Sánchez5Department of Molecular Biomedicine, Centro de Investigaciones Biológicas-Margarita Salas (CSIC), 28040 Madrid, SpainCentro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid, SpainNeurovascular Research Unit, Department of Pharmacology and Toxicology, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartment of System Biology, Facultad de Medicina, Universidad de Alcalá, 28805 Alcalá de Henares, SpainDepartment of Molecular Biomedicine, Centro de Investigaciones Biológicas-Margarita Salas (CSIC), 28040 Madrid, SpainDepartment of Molecular Biomedicine, Centro de Investigaciones Biológicas-Margarita Salas (CSIC), 28040 Madrid, SpainAlthough considered a rare retinal dystrophy, retinitis pigmentosa (RP) is the primary cause of hereditary blindness. Given its diverse genetic etiology (>3000 mutations in >60 genes), there is an urgent need for novel treatments that target common features of the disease. TLR2 is a key activator of innate immune response. To examine its role in RP progression we characterized the expression profile of <i>Tlr2</i> and its adaptor molecules and the consequences of <i>Tlr2</i> deletion in two genetically distinct models of RP: <i>Pde6b<sup>rd10/rd10</sup></i> (<i>rd10</i>) and <i>Rho<sup>P23H/+</sup></i> (<i>P23H/+</i>) mice. In both models, expression levels of <i>Tlr2</i> and its adaptor molecules increased in parallel with those of the proinflammatory cytokine <i>Il1b</i>. In <i>rd10</i> mice, deletion of a single <i>Tlr2</i> allele had no effect on visual function, as evaluated by electroretinography. However, in both RP models, complete elimination of <i>Tlr2</i> attenuated the loss of visual function and mitigated the loss of photoreceptor cell numbers. In <i>Tlr2</i> null <i>rd10</i> mice, we observed decreases in the total number of microglial cells, assessed by flow cytometry, and in the number of microglia infiltrating the photoreceptor layers. Together, these results point to TLR2 as a mutation-independent therapeutic target for RP.https://www.mdpi.com/1422-0067/22/15/7815retinitis pigmentosaretinaTLRTLR2microgliainnate immunity |
| spellingShingle | Alonso Sánchez-Cruz Andrea C. Méndez Ignacio Lizasoain Pedro de la Villa Enrique J. de la Rosa Catalina Hernández-Sánchez <i>Tlr2</i> Gene Deletion Delays Retinal Degeneration in Two Genetically Distinct Mouse Models of Retinitis Pigmentosa International Journal of Molecular Sciences retinitis pigmentosa retina TLR TLR2 microglia innate immunity |
| title | <i>Tlr2</i> Gene Deletion Delays Retinal Degeneration in Two Genetically Distinct Mouse Models of Retinitis Pigmentosa |
| title_full | <i>Tlr2</i> Gene Deletion Delays Retinal Degeneration in Two Genetically Distinct Mouse Models of Retinitis Pigmentosa |
| title_fullStr | <i>Tlr2</i> Gene Deletion Delays Retinal Degeneration in Two Genetically Distinct Mouse Models of Retinitis Pigmentosa |
| title_full_unstemmed | <i>Tlr2</i> Gene Deletion Delays Retinal Degeneration in Two Genetically Distinct Mouse Models of Retinitis Pigmentosa |
| title_short | <i>Tlr2</i> Gene Deletion Delays Retinal Degeneration in Two Genetically Distinct Mouse Models of Retinitis Pigmentosa |
| title_sort | i tlr2 i gene deletion delays retinal degeneration in two genetically distinct mouse models of retinitis pigmentosa |
| topic | retinitis pigmentosa retina TLR TLR2 microglia innate immunity |
| url | https://www.mdpi.com/1422-0067/22/15/7815 |
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