ArticleJCI insight2023
Gene augmentation of LCA5-associated Leber congenital amaurosis ameliorates bulge region defects of the photoreceptor ciliary axoneme.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Recovery of cone-mediated vision in Lebercilin associated retinal ciliopathy after gene therapy: One-year results of a phase I/II trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Trial
- Low-pass whole-genome sequencing reveals genomic diversity and ecotype-specific adaptation in indigenous Tigrayan chickens.Scientific reports · 2026Article
- HAK-actin, a U-ExM-compatible probe to image the actin cytoskeleton.Cell reports methods · 2026Article
- Primary cilia gene defects in BMSCs induce idiopathic scoliosis.Cellular and molecular life sciences : CMLS · 2025Article
- Advances in high-resolution imaging of centrioles and cilia.Journal of cell science · 2025Review
- Tackling ciliary specialization to understand phenotypic variability in human primary ciliopathies.Journal of cell science · 2025Review
- Sub-ciliary localization of CEP290 and effects of its loss in mouse photoreceptors during development.Journal of cell science · 2025Article
- Advances in ciliary proteomics - towards cracking the hidden proteome code of cilia.Journal of cell science · 2025Review
- Mapping Protein Distribution in the Canine Photoreceptor Sensory Cilium and Calyceal Processes by Ultrastructure Expansion Microscopy.Investigative ophthalmology & visual science · 2025Article
- Ciliopathy-associated protein, CEP290, is required for ciliary necklace and outer segment membrane formation in retinal photoreceptors.bioRxiv : the preprint server for biology · 2025Article
- Glutamylation imbalance impairs the molecular architecture of the photoreceptor cilium.The EMBO journal · 2024Article
- Mapping protein distribution in the canine photoreceptor sensory cilium and calyceal processes by ultrastructure expansion microscopy.bioRxiv : the preprint server for biology · 2024Article
- Fine-tuning FAM161A gene augmentation therapy to restore retinal function.EMBO molecular medicine · 2024Article
- iU-ExM: nanoscopy of organelles and tissues with iterative ultrastructure expansion microscopy.Nature communications · 2023Article
- Clinical and Molecular Aspects of C2orf71/PCARE in Retinal Diseases.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leber congenital amaurosis (LCA) is a group of inherited retinal diseases characterized by early-onset, rapid loss of photoreceptor cells. Despite the discovery of a growing number of genes associated with this disease, the molecular mechanisms of photoreceptor cell degeneration of most LCA subtypes remain poorly understood. Here, using retina-specific affinity proteomics combined with ultrastructure expansion microscopy, we reveal the structural and molecular defects underlying LCA type 5 (LCA5) with nanoscale resolution. We show that LCA5-encoded lebercilin, together with retinitis pigmentosa 1 protein (RP1) and the intraflagellar transport (IFT) proteins IFT81 and IFT88, localized at the bulge region of the photoreceptor outer segment (OS), a region crucial for OS membrane disc formation. Next, we demonstrate that mutant mice deficient in lebercilin exhibited early axonemal defects at the bulge region and the distal OS, accompanied by reduced levels of RP1 and IFT proteins, affecting membrane disc formation and presumably leading to photoreceptor death. Finally, adeno-associated virus-based LCA5 gene augmentation partially restored the bulge region, preserved OS axoneme structure and membrane disc formation, and resulted in photoreceptor cell survival. Our approach thus provides a next level of assessment of retinal (gene) therapy efficacy at the molecular level.
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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.