ArticleJCI insight2021
REP1 deficiency causes systemic dysfunction of lipid metabolism and oxidative stress in choroideremia.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Metabolomic signatures suggest altered bile acid and energy metabolism in CRB1- retinopathies.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- REP-1 deficiency induces aberrant mitochondrial metabolic rewiring from glycolysis to lipid oxidation in CHM disease.Cell death & disease · 2026Article
- Partial Serotonin Transporter Deficiency Modulates Plasma Metabolome, Arginine-Nitric Oxide Pathway and Emotional Behavior in Mice Exposed to Western Diet.Metabolites · 2026Article
- Genetic Analysis of Choroideremia-Related Rab Escort Proteins.International journal of molecular sciences · 2025Article
- Review
- Oxidative Stress, Inflammation and Altered Glucose Metabolism Contribute to the Retinal Phenotype in the Choroideremia Zebrafish.Antioxidants (Basel, Switzerland) · 2024Article
- Loss of REP1 impacts choroidal melanogenesis and vasculogenesis in choroideremia.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Retinal vascular reactivity in carriers of X-linked inherited retinal disease - a study using optical coherence tomography angiography.Frontiers in ophthalmology · 2024Article
- Updates on protein-prenylation and associated inherited retinopathies.Frontiers in ophthalmology · 2024Review
- Choroideremia: The Endpoint Endgame.International journal of molecular sciences · 2023Review
- Oxidative and Endoplasmic Reticulum Stress Represent Novel Therapeutic Targets for Choroideremia.Antioxidants (Basel, Switzerland) · 2023Article
- Choroideremia: Toward Regulatory Approval of Retinal Gene Therapy.Cold Spring Harbor perspectives in medicine · 2023Article
- Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.Signal transduction and targeted therapy · 2023Review
- US Health Resource Utilization and Cost Burden Associated with Choroideremia.Clinical ophthalmology (Auckland, N.Z.) · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Choroideremia (CHM) is an X-linked recessive chorioretinal dystrophy caused by mutations in CHM, encoding for Rab escort protein 1 (REP1). Loss of functional REP1 leads to the accumulation of unprenylated Rab proteins and defective intracellular protein trafficking, the putative cause for photoreceptor, retinal pigment epithelium (RPE), and choroidal degeneration. CHM is ubiquitously expressed, but adequate prenylation is considered to be achieved, outside the retina, through the isoform REP2. Recently, the possibility of systemic features in CHM has been debated; therefore, in this study, whole metabolomic analysis of plasma samples from 25 CHM patients versus age- and sex-matched controls was performed. Results showed plasma alterations in oxidative stress-related metabolites, coupled with alterations in tryptophan metabolism, leading to significantly raised serotonin levels. Lipid metabolism was disrupted with decreased branched fatty acids and acylcarnitines, suggestive of dysfunctional lipid oxidation, as well as imbalances of several sphingolipids and glycerophospholipids. Targeted lipidomics of the chmru848 zebrafish provided further evidence for dysfunction, with the use of fenofibrate over simvastatin circumventing the prenylation pathway to improve the lipid profile and increase survival. This study provides strong evidence for systemic manifestations of CHM and proposes potentially novel pathomechanisms and targets for therapeutic consideration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.