ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
PSCs Reveal PUFA-Provoked Mitochondrial Stress as a Central Node Potentiating RPE Degeneration in Bietti's Crystalline Dystrophy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Gene replacement therapy in Bietti crystalline corneoretinal dystrophy: an open-label, single-arm, exploratory trial.Signal transduction and targeted therapy · 2024Trial
- Integrated transcriptomic and metabolomic analyses reveal distinct energy metabolic signatures and functional properties of RPE cells under two culture conditions.Scientific reports · 2026Article
- The role of full-field stimulus threshold in evaluating Bietti crystalline dystrophy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Observational
- Comprehensive genotypic and phenotypic analysis of Bietti crystalline dystrophy: insights from a large cohort study.Science China. Life sciences · 2025Observational
- Infantile Cerebellar-Retinal Degeneration Associated With Novel ACO2 Variants: Clinical Features and Insights From a Drosophila Model.Clinical genetics · 2025Article
- Preclinical studies of an AAV8-CYP4V2 gene therapy VGR-R01 for the treatment of Bietti crystalline dystrophy.Molecular therapy. Methods & clinical development · 2025Article
- A 30-year-old man with Bietti crystalline dystrophy:a rare case report from Syria.Annals of medicine and surgery (2012) · 2025Article
- Safety and Vision Outcomes Following Gene Therapy for Bietti Crystalline Dystrophy: A Nonrandomized Clinical Trial.JAMA ophthalmology · 2025Article
- Bietti crystalline corneoretinal dystrophy: Advances in understanding and gene therapeutic approaches.Molecular vision · 2025Review
- Targeted lipidomics uncovers oxylipin perturbations and potential circulation biomarkers in Bietti's crystalline dystrophy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024Article
- Investigating Microperimetric Features in Bietti Crystalline Dystrophy Patients: A Cross-Sectional Longitudinal Study in a Large Cohort.Investigative ophthalmology & visual science · 2024Article
- The retinal pigment epithelium: Functions and roles in ocular diseases.Fundamental research · 2024Review
- Evaluating precision medicine approaches for gene therapy in patient-specific cellular models of Bietti crystalline dystrophy.JCI insight · 2024Article
- Uncovering the role of ferroptosis in Bietti crystalline dystrophy and potential therapeutic strategies.Cell communication and signaling : CCS · 2024Article
- In vivo genome editing via CRISPR/Cas9-mediated homology-independent targeted integration for Bietti crystalline corneoretinal dystrophy treatment.Nature communications · 2024Article
- Mesenchymal Stem Cell-Derived Mitochondria Enhance Extracellular Matrix-Derived Grafts for the Repair of Nerve Defect.Advanced healthcare materials · 2024Article
- Optical coherence tomography angiography in Bietti crystalline dystrophy.European journal of ophthalmology · 2023Article
- A patient advocating for transparent science in rare disease research.Orphanet journal of rare diseases · 2023Article
- Diagnostic and Management Strategies of Bietti Crystalline Dystrophy: Current Perspectives.Clinical ophthalmology (Auckland, N.Z.) · 2023Review
- A Bietti Crystalline Dystrophy Mouse Model Shows Increased Sensitivity to Light-Induced Injury.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bietti's crystalline dystrophy (BCD) is an incurable retinal disorder caused by the polypeptide 2 of cytochrome P450 family 4 subfamily V (CYP4V2) mutations. Patients with BCD present degeneration of retinal pigmented epithelial (RPE) cells and consequent blindness. The lack of appropriate disease models and patients' RPE cells limits our understanding of the pathological mechanism of RPE degeneration. In this study, using CYP4V2 mutant pluripotent stem cells as disease models, we demonstrated that RPE cells with CYP4V2 mutations presented a disrupted fatty acid homeostasis, which were characterized with excessive accumulation of poly-unsaturated fatty acid (PUFA), including arachidonic acid (AA) and eicosapentaenoic acid (EPA). The PUFA overload increased mitochondrial reactive oxygen species, impaired mitochondrial respiratory functions, and triggered mitochondrial stress-activated p53-independent apoptosis in CYP4V2 mutant RPE cells. Restoration of the mutant CYP4V2 using adeno-associated virus 2 (AAV2) can effectively reduce PUFA deposition, alleviate mitochondria oxidative stresses, and rescue RPE cell death in BCD RPE cells. Taken together, our results highlight a role of PUFA-induced mitochondrial damage as a central node to potentiate RPE degeneration in BCD patients. AAV2-mediated gene therapy may represent a feasible strategy for the treatment of BCD.
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