PUBLICATION
Oxidative Stress, Inflammation and Altered Glucose Metabolism Contribute to the Retinal Phenotype in the Choroideremia Zebrafish
- Authors
- Méjécase, C., Nair, N., Sarkar, H., Soro-Barrio, P., Toms, M., Halliday, S., Linkens, K., Jaroszynska, N., Maurer, C., Owen, N., Moosajee, M.
- ID
- ZDB-PUB-250109-182
- Date
- 2024
- Source
- Antioxidants (Basel, Switzerland) 13(12): (Journal)
- Registered Authors
- Keywords
- CHM, choroideremia, glucose metabolism, inherited retinal diseases, oxidative stress, zebrafish
- MeSH Terms
- none
- PubMed
- 39765914 Full text @ Antioxidants (Basel)
Citation
Méjécase, C., Nair, N., Sarkar, H., Soro-Barrio, P., Toms, M., Halliday, S., Linkens, K., Jaroszynska, N., Maurer, C., Owen, N., Moosajee, M. (2024) Oxidative Stress, Inflammation and Altered Glucose Metabolism Contribute to the Retinal Phenotype in the Choroideremia Zebrafish. Antioxidants (Basel, Switzerland). 13(12):.
Abstract
Reactive oxygen species (ROS) within the retina play a key role in maintaining function and cell survival. However, excessive ROS can lead to oxidative stress, inducing dysregulation of metabolic and inflammatory pathways. The chmru848 zebrafish models choroideremia (CHM), an X-linked chorioretinal dystrophy, which predominantly affects the photoreceptors, retinal pigment epithelium (RPE), and choroid. In this study, we examined the transcriptomic signature of the chmru848 zebrafish retina to reveal the upregulation of cytokine pathways and glia migration, upregulation of oxidative, ER stress and apoptosis markers, and the dysregulation of glucose metabolism with the downregulation of glycolysis and the upregulation of the oxidative phase of the pentose phosphate pathway. Glucose uptake was impaired in the chmru848 retina using the 2-NBDG glucose uptake assay. Following the overexpression of human PFKM, partial rescue was seen with the preservation of photoreceptors and RPE and increased glucose uptake, but without modifying glycolysis and oxidative stress markers. Therapies targeting glucose metabolism in CHM may represent a potential remedial approach.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping