Title | Ceramide compensation by ceramide synthases preserves retinal function and structure in a retinal dystrophy mouse model. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Qian, X, Srinivasan, T, He, J, Lu, J, Jin, Y, Gu, H, Chen, R |
Journal | Dis Model Mech |
Volume | 16 |
Issue | 7 |
Date Published | 2023 Jul 01 |
ISSN | 1754-8411 |
Keywords | Animals, Ceramides, Mice, Oxidoreductases, Retina, Retinal Dystrophies |
Abstract | 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. |
DOI | 10.1242/dmm.050168 |
Alternate Journal | Dis Model Mech |
PubMed ID | 37466006 |
PubMed Central ID | PMC10387349 |
Grant List | R01 EY018571 / EY / NEI NIH HHS / United States R01 EY020540 / EY / NEI NIH HHS / United States R01 EY022356 / EY / NEI NIH HHS / United States |
Ceramide compensation by ceramide synthases preserves retinal function and structure in a retinal dystrophy mouse model.
Similar Publications
PRL1 and PRL3 promote macropinocytosis via its lipid phosphatase activity. Theranostics. 2024;14(9):3423-3438. | .
Genetic diversity of 1,845 rhesus macaques improves genetic variation interpretation and identifies disease models. Nat Commun. 2024;15(1):5658. | .
A single cell RNA sequence atlas of the early Drosophila larval eye. BMC Genomics. 2024;25(1):616. | .