ArticleProceedings of the National Academy of Sciences of the United States of America2015
Bestrophin 1 is indispensable for volume regulation in human retinal pigment epithelium cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 120 citations in OpenAlex.
- Evaluation of the Toxicity and Efficacy of an Adeno-Associated Viral Vector ExpressingHuman gene therapy · 2026Article
- Review of the clinical electrooculogram - Part 1: Mechanism of the Light-Rise.Documenta ophthalmologica. Advances in ophthalmology · 2026Review
- Review of the clinical electrooculogram - Part 2: the bestrophinopathies and modified protocols.Documenta ophthalmologica. Advances in ophthalmology · 2026Review
- Allele-specific suppression of pathogenic bestrophin-1 transcripts by CRISPR/Cas9-mediated genome editing.Genome medicine · 2026Article
- Glial Ion Channels in Myelin Pathophysiology: Insights from Leukodystrophies.Life (Basel, Switzerland) · 2025Review
- Novel BEST1 Variant Characterization in a Large French Cohort in Light of Updated Bestrophin-1 Structure-Function Correlation.Investigative ophthalmology & visual science · 2025Article
- A quantitative analysis of bestrophin 1 cellular localization in mouse cerebral cortex.Acta physiologica (Oxford, England) · 2025Article
- Ion channels research in hPSC-RPE cells: bridging benchwork to clinical applications.Journal of translational medicine · 2024Review
- Retinal response to light exposure in BEST1-mutant dogs evaluated with ultra-high resolution OCT.Vision research · 2024Article
- Elemental mass spectrometry to study metallo-transcriptomic changes during the in vitro degeneration of the retinal pigment epithelium.Analytical and bioanalytical chemistry · 2024Article
- Modeling inherited retinal diseases using human induced pluripotent stem cell derived photoreceptor cells and retinal pigment epithelial cells.Frontiers in medicine · 2024Review
- The Key Role of Astrocytes in Amyotrophic Lateral Sclerosis and Their Commitment to Glutamate Excitotoxicity.International journal of molecular sciences · 2023Review
- A simple, rapid fluorescent reporter-based method for detection of ectopic cre recombinase expression in presumed retinal cell type-targeted mouse lines.Experimental eye research · 2023Article
- Comprehensive Genetic Analysis Unraveled the Missing Heritability and a Founder Variant of BEST1 in a Chinese Cohort With Autosomal Recessive Bestrophinopathy.Investigative ophthalmology & visual science · 2023Article
- BEST1 Positive Monocytes in Circulation: Visualize Intratumoral Crosstalk between Cancer Cells and Monocytes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Cellular and Molecular Mechanisms of Pathogenesis Underlying Inherited Retinal Dystrophies.Biomolecules · 2023Review
- Autosomal Dominant Vitreoretinochoroidopathy With a Novel BEST1 Mutation and a Review of Reported Mutations.Cureus · 2022Article
- Clinical Correlation Between Optical Coherence Tomography Biomarkers and Retinal Sensitivity in Best Vitelliform Macular Dystrophy.Translational vision science & technology · 2022Observational
- Deep learning to distinguish Best vitelliform macular dystrophy (BVMD) from adult-onset vitelliform macular degeneration (AVMD).Scientific reports · 2022Article
- Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders.Cells · 2022Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In response to cell swelling, volume-regulated anion channels (VRACs) participate in a process known as regulatory volume decrease (RVD). Only recently, first insight into the molecular identity of mammalian VRACs was obtained by the discovery of the leucine-rich repeats containing 8A (LRRC8A) gene. Here, we show that bestrophin 1 (BEST1) but not LRRC8A is crucial for volume regulation in human retinal pigment epithelium (RPE) cells. Whole-cell patch-clamp recordings in RPE derived from human-induced pluripotent stem cells (hiPSC) exhibit an outwardly rectifying chloride current with characteristic functional properties of VRACs. This current is severely reduced in hiPSC-RPE cells derived from macular dystrophy patients with pathologic BEST1 mutations. Disruption of the orthologous mouse gene (Best1(-/-)) does not result in obvious retinal pathology but leads to a severe subfertility phenotype in agreement with minor endogenous expression of Best1 in murine RPE but highly abundant expression in mouse testis. Sperm from Best1(-/-) mice showed reduced motility and abnormal sperm morphology, indicating an inability in RVD. Together, our data suggest that the molecular identity of VRACs is more complex--that is, instead of a single ubiquitous channel, VRACs could be formed by cell type- or tissue-specific subunit composition. Our findings provide the basis to further examine VRAC diversity in normal and diseased cell physiology, which is key to exploring novel therapeutic approaches in VRAC-associated pathologies.
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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.