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Ceramide compensation by ceramide synthases preserves retinal function and structure in a retinal dystrophy mouse model
Increasing evidence has supported the role of ceramide as a mediator of photoreceptor dysfunction or cell death in ceramide accumulation and deficiency contexts. TLCD3B, a non-canonical ceramide synthase, was previously identified in addition to the six canonical ceramide synthases (CerSs), and the...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The Company of Biologists Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10387349/ https://www.ncbi.nlm.nih.gov/pubmed/37466006 http://dx.doi.org/10.1242/dmm.050168 |
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author | Qian, Xinye Srinivasan, Tanmay He, Jessica Lu, Jiaxiong Jin, Yan Gu, Haiwei Chen, Rui |
author_facet | Qian, Xinye Srinivasan, Tanmay He, Jessica Lu, Jiaxiong Jin, Yan Gu, Haiwei Chen, Rui |
author_sort | Qian, Xinye |
collection | PubMed |
description | Increasing evidence has supported the role of ceramide as a mediator of photoreceptor dysfunction or cell death in ceramide accumulation and deficiency contexts. TLCD3B, a non-canonical ceramide synthase, was previously identified in addition to the six canonical ceramide synthases (CerSs), and the Tlcd3b(−/−) mouse model exhibited both retinal dysfunction and degeneration. As previous canonical CerS-deficient mouse models failed to display retinal degeneration, the mechanisms of how TLCD3B interacts with CerSs have not been investigated. Additionally, as the ceramide profile of each CerS is distinct, it is unclear whether the overall level or the homeostasis of different ceramide species plays a critical role in photoreceptor degeneration. Interactions between TLCD3B with canonical CerSs expressed in the retina were examined by subretinally injecting recombinant adeno-associated virus 8 vectors containing the Cers2 (rAAV8-CerS2), Cers4 (rAAV8-CerS4) and Cers5 (rAAV8-CerS5) genes. Injection of all three rAAV8-CerS vectors restored retinal functions as indicated by improved electroretinogram responses, but only rAAV8-CerS5 successfully retained retinal morphology in Tlcd3b(−/−) mice. CerSs and TLCD3B played partially redundant roles. Additionally, rather than acting as an integral entity, different ceramide species had different impacts on retinal cells, suggesting that the maintenance of the overall ceramide profile is critical for retinal function. |
format | Online Article Text |
id | pubmed-10387349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-103873492023-07-31 Ceramide compensation by ceramide synthases preserves retinal function and structure in a retinal dystrophy mouse model Qian, Xinye Srinivasan, Tanmay He, Jessica Lu, Jiaxiong Jin, Yan Gu, Haiwei Chen, Rui Dis Model Mech Research Article Increasing evidence has supported the role of ceramide as a mediator of photoreceptor dysfunction or cell death in ceramide accumulation and deficiency contexts. TLCD3B, a non-canonical ceramide synthase, was previously identified in addition to the six canonical ceramide synthases (CerSs), and the Tlcd3b(−/−) mouse model exhibited both retinal dysfunction and degeneration. As previous canonical CerS-deficient mouse models failed to display retinal degeneration, the mechanisms of how TLCD3B interacts with CerSs have not been investigated. Additionally, as the ceramide profile of each CerS is distinct, it is unclear whether the overall level or the homeostasis of different ceramide species plays a critical role in photoreceptor degeneration. Interactions between TLCD3B with canonical CerSs expressed in the retina were examined by subretinally injecting recombinant adeno-associated virus 8 vectors containing the Cers2 (rAAV8-CerS2), Cers4 (rAAV8-CerS4) and Cers5 (rAAV8-CerS5) genes. Injection of all three rAAV8-CerS vectors restored retinal functions as indicated by improved electroretinogram responses, but only rAAV8-CerS5 successfully retained retinal morphology in Tlcd3b(−/−) mice. CerSs and TLCD3B played partially redundant roles. Additionally, rather than acting as an integral entity, different ceramide species had different impacts on retinal cells, suggesting that the maintenance of the overall ceramide profile is critical for retinal function. The Company of Biologists Ltd 2023-07-19 /pmc/articles/PMC10387349/ /pubmed/37466006 http://dx.doi.org/10.1242/dmm.050168 Text en © 2023. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Qian, Xinye Srinivasan, Tanmay He, Jessica Lu, Jiaxiong Jin, Yan Gu, Haiwei Chen, Rui Ceramide compensation by ceramide synthases preserves retinal function and structure in a retinal dystrophy mouse model |
title | Ceramide compensation by ceramide synthases preserves retinal function and structure in a retinal dystrophy mouse model |
title_full | Ceramide compensation by ceramide synthases preserves retinal function and structure in a retinal dystrophy mouse model |
title_fullStr | Ceramide compensation by ceramide synthases preserves retinal function and structure in a retinal dystrophy mouse model |
title_full_unstemmed | Ceramide compensation by ceramide synthases preserves retinal function and structure in a retinal dystrophy mouse model |
title_short | Ceramide compensation by ceramide synthases preserves retinal function and structure in a retinal dystrophy mouse model |
title_sort | ceramide compensation by ceramide synthases preserves retinal function and structure in a retinal dystrophy mouse model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10387349/ https://www.ncbi.nlm.nih.gov/pubmed/37466006 http://dx.doi.org/10.1242/dmm.050168 |
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