ArticleInvestigative ophthalmology & visual science2008
Transgenic mice expressing the Tyr437His mutant of human myocilin protein develop glaucoma.
Article in Investigative ophthalmology & visual science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 3 of them syntheses that pooled it.
What it found
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The trial behind it
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Who cites it
86 citing papers in PubMed, 3 syntheses or guidelines pooled it, 141 citations in OpenAlex.
- Effect of genotype on individual response to the pharmacological treatment of glaucoma: a systematic review and meta-analysis.Biology direct · 2023Pooled it
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- No association of genetic polymorphisms in CYP1B1 with primary open-angle glaucoma: a meta- and gene-based analysis.Molecular vision · 2012Pooled it
- Disease modeling of myocilin mutation-dependent normal tension glaucoma: human retinal ganglion cell susceptibility to unfolded protein response and mTOR signaling.Stem cells (Dayton, Ohio) · 2026Article
- Rodent Models of Glaucoma: How Mice and Rats Can Help Human Vision Move Out of the Woods and Into the Light.Cells · 2025Review
- Longitudinal Structural and Microvascular Imaging of Mouse Retina After Optic Nerve Crush Using Temporal Speckle-Averaging Visible Light OCT.Investigative ophthalmology & visual science · 2025Article
- Serine to proline mutation at position 341 of MYOC impairs trabecular meshwork function by causing autophagy deregulation.Cell death discovery · 2024Article
- Therapeutic strategies for glaucoma and optic neuropathies.Molecular aspects of medicine · 2023Review
- Human Pro370Leu Mutant Myocilin Induces the Phenotype of Open-Angle Glaucoma in Transgenic Mice.Cellular and molecular neurobiology · 2023Article
- Article
- Transgenic Overexpression of Myocilin Leads to Variable Ocular Anterior Segment and Retinal Alterations Associated with Extracellular Matrix Abnormalities in Adult Zebrafish.International journal of molecular sciences · 2022Article
- Genome-wide DNA methylation and gene expression patterns of androgenetic haploid tiger pufferfish (Takifugu rubripes) provide insights into haploid syndrome.Scientific reports · 2022Article
- Differential Retinal Ganglion Cell Vulnerability, A Critical Clue for the Identification of Neuroprotective Genes in Glaucoma.Frontiers in ophthalmology · 2022Review
- Myocilin Gene Mutation Induced Autophagy Activation Causes Dysfunction of Trabecular Meshwork Cells.Frontiers in cell and developmental biology · 2022Article
- Looking for In Vitro Models for Retinal Diseases.International journal of molecular sciences · 2021Review
- Common and rare myocilin variants: Predicting glaucoma pathogenicity based on genetics, clinical, and laboratory misfolding data.Human mutation · 2021Review
- Autophagy stimulation reduces ocular hypertension in a murine glaucoma model via autophagic degradation of mutant myocilin.JCI insight · 2021Article
- Article
- Elevated Hydrostatic Pressure Causes Retinal Degeneration Through Upregulating Lipocalin-2.Frontiers in cell and developmental biology · 2021Article
- Physiologic Consequences of Caveolin-1 Ablation in Conventional Outflow Endothelia.Investigative ophthalmology & visual science · 2020Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo developed a genetic mouse model of primary open-angle glaucoma induced by expression of mutated human myocilin in transgenic mice and to test whether expression of mutated human myocilin in the eye angle structures produces more significant damage to the eye than does mutated mouse myocilin.
methodsRecombineering in Escherichia coli was used to introduce the Tyr437His point mutation into a BAC carrying the full-length human MYOCILIN (MYOC) gene and long flanking regions. This BAC was used to produce transgenic mice. The expression of myocilin in the iridocorneal angle tissues and aqueous humor was studied by immunohistochemistry and Western blot analysis. Intraocular pressure was measured noninvasively with a fiber optic transducer. Retinal ganglion cells were retrograde labeled with fluorescent gold, and counted 5 days after labeling.
resultsBAC transgenic mice expressed elevated levels of myocilin in tissues of the iridocorneal angle. Expression of mutated myocilin induced its intracellular accumulation and prevented secretion of both mutated and wild-type myocilin into the aqueous humor. Transgenic mice demonstrated a moderate elevation of intraocular pressure, which was more pronounced at night than in daytime. In the peripheral retina, transgenic mice lost 20% of the retinal ganglion cells and 55% of large retinal ganglion cells. Axonal degeneration was observed at the periphery of the optic nerve.
conclusionsExpression of equivalent levels of mutated human or mouse myocilin in the eyes of transgenic mice produce comparable pathologic changes that are similar to those observed in patients with glaucoma.
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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.