ArticlePLoS genetics2011
Mutations in zebrafish lrp2 result in adult-onset ocular pathogenesis that models myopia and other risk factors for glaucoma.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma.PLoS genetics · 2012Pooled it
- Article
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- Contributions of aquatic organisms to understanding the vertebrate ocular lens.Frontiers in ophthalmology · 2026Review
- Independent Mutations in theInternational journal of molecular sciences · 2025Article
- Increasing the diagnostic yield of childhood glaucoma cases recruited into the 100,000 Genomes Project.BMC genomics · 2024Article
- Exploring the origin of a unique mutant allele in twin-tail goldfish using CRISPR/Cas9 mutants.Scientific reports · 2024Article
- The Goldfish Genome and Its Utility for Understanding Gene Regulation and Vertebrate Body Morphology.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Studying zebrafish nervous system structure and function in health and disease with electron microscopy.Development, growth & differentiation · 2023Review
- Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium.Molecular neurodegeneration · 2023Review
- Variants of LRP2, encoding a multifunctional cell-surface endocytic receptor, associated with hearing loss and retinal dystrophy.Clinical genetics · 2023Article
- A temporal single cell transcriptome atlas of zebrafish anterior segment development.Scientific reports · 2023Article
- An Overview towards Zebrafish Larvae as a Model for Ocular Diseases.International journal of molecular sciences · 2023Review
- Behavioral Phenotype, Electroclinical Features, and Treatment Options in Twins withCase reports in genetics · 2023Article
- Socs3b regulates the development and function of innate immune cells in zebrafish.Frontiers in immunology · 2023Article
- Causal gene identification and desirable trait recreation in goldfish.Science China. Life sciences · 2022Article
- Lrpap1 deficiency leads to myopia through TGF-β-induced apoptosis in zebrafish.Cell communication and signaling : CCS · 2022Article
- Assessment of endocytic traffic and Ocrl function in the developing zebrafish neuroepithelium.Journal of cell science · 2022Article
- Vascular endothelial growth factor from retinal pigment epithelium is essential in choriocapillaris and axial length maintenance.PNAS nexus · 2022Article
- Quantitative proteomics analysis of human vitreous in rhegmatogenous retinal detachment associated with choroidal detachment by data-independent acquisition mass spectrometry.Molecular and cellular biochemistry · 2022Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
Abstract
The glaucomas comprise a genetically complex group of retinal neuropathies that typically occur late in life and are characterized by progressive pathology of the optic nerve head and degeneration of retinal ganglion cells. In addition to age and family history, other significant risk factors for glaucoma include elevated intraocular pressure (IOP) and myopia. The complexity of glaucoma has made it difficult to model in animals, but also challenging to identify responsible genes. We have used zebrafish to identify a genetically complex, recessive mutant that shows risk factors for glaucoma including adult onset severe myopia, elevated IOP, and progressive retinal ganglion cell pathology. Positional cloning and analysis of a non-complementing allele indicated that non-sense mutations in low density lipoprotein receptor-related protein 2 (lrp2) underlie the mutant phenotype. Lrp2, previously named Megalin, functions as an endocytic receptor for a wide-variety of bioactive molecules including Sonic hedgehog, bone morphogenic protein 4, retinol-binding protein, vitamin D-binding protein, and apolipoprotein E, among others. Detailed phenotype analyses indicated that as lrp2 mutant fish age, many individuals--but not all--develop high IOP and severe myopia with obviously enlarged eye globes. This results in retinal stretch and prolonged stress to retinal ganglion cells, which ultimately show signs of pathogenesis. Our studies implicate altered Lrp2-mediated homeostasis as important for myopia and other risk factors for glaucoma in humans and establish a new genetic model for further study of phenotypes associated with this disease.
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Registered trials
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