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Oxidative stress, altered glucose metabolism and inflammation contribute to the retinal phenotype in the choroideremia zebrafish

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 upregulation of cytokine pathways and glia migration, upregulation of oxidative, ER stress and apoptosis markers, and dysregulation of glucose metabolism with downregulation of glycolysis and upregulation of the oxidative phase of the pentose phosphate pathway. Glucose uptake was overall impaired in the chmru848 retina using the 2-NBDG glucose uptake assay, but after overexpression of human PFKM, it partially rescued the retinal phenotype and glucose uptake, but without modifying the expression of glycolysis markers. Therapies targeting glucose metabolism in CHM may represent a potential remedial approach.

ORGANISM(S): Danio rerio

PROVIDER: GSE254948 | GEO | 2025/01/02

REPOSITORIES: GEO

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