PUBLICATION
Deciphering the pathogenesis of retinopathy associated with carnitine palmitoyltransferase I deficiency in zebrafish model
- Authors
- Ulhaq, Z.S., Ogino, Y., Tse, W.K.F.
- ID
- ZDB-PUB-230505-43
- Date
- 2023
- Source
- Biochemical and Biophysical Research Communications 664: 100107100-107 (Journal)
- Registered Authors
- Tse, Ka Fai William, Ulhaq, Zulvikar Syambani
- Keywords
- Ciliopathies, Fatty acid oxidation disorders, Ferroptosis, Photoreceptor degeneration
- MeSH Terms
-
- Animals
- Carnitine/metabolism
- Carnitine O-Palmitoyltransferase/genetics
- Carnitine O-Palmitoyltransferase/metabolism
- Fatty Acids/metabolism
- Oxidation-Reduction
- Retinal Diseases*/etiology
- Zebrafish*/metabolism
- PubMed
- 37141637 Full text @ Biochem. Biophys. Res. Commun.
Citation
Ulhaq, Z.S., Ogino, Y., Tse, W.K.F. (2023) Deciphering the pathogenesis of retinopathy associated with carnitine palmitoyltransferase I deficiency in zebrafish model. Biochemical and Biophysical Research Communications. 664:100107100-107.
Abstract
Fatty acid oxidation disorders (FAODs) are a group of rare genetic metabolic disorders caused by mutations in genes responsible for transporting and metabolizing fatty acids in the mitochondria. One crucial enzyme involved in this process is carnitine palmitoyltransferase I (CPT1), which transports long-chain fatty acids to the mitochondrial matrix for beta-oxidation. Defects in beta-oxidation enzymes often lead to pigmentary retinopathy; however, the underlying mechanisms are not entirely understood. To investigate FAOD and its impact on the retina, we employed zebrafish as a model organism. Specifically, we used antisense-mediated knockdown strategies to target the cpt1a gene and examined the resulting retinal phenotypes. We demonstrated that the cpt1a MO-injected fish significantly reduced the length of connecting cilia and severely affected photoreceptor cell development. Moreover, our findings highlight that the loss of functional cpt1a disrupted energy homeostasis in the retina, leading to lipid droplet deposition and promoting ferroptosis, which is likely attributed to the photoreceptor degeneration and visual impairments observed in the cpt1a morphants.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping