ArticlePloS one2009
Overexpression of myocilin in the Drosophila eye activates the unfolded protein response: implications for glaucoma.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 44 citations in OpenAlex.
- Multi-omics Mendelian randomization analysis identifies SPATA20 as a cross-omic target in primary open angle glaucoma.International journal of ophthalmology · 2026Article
- Exploring the Genetic Landscape of Childhood Glaucoma.Children (Basel, Switzerland) · 2024Review
- Somatic Mutations within Myocilin due to Aging May Be a Potential Risk Factor for Glaucoma.Genes · 2024Article
- Review
- 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
- Screening of the Drug-Induced Effects of Prostaglandin EP2 and FP Agonists on 3D Cultures of Dexamethasone-Treated Human Trabecular Meshwork Cells.Biomedicines · 2021Article
- The Potential Role of Small-Molecule PERK Inhibitor LDN-0060609 in Primary Open-Angle Glaucoma Treatment.International journal of molecular sciences · 2021Article
- Heat shock proteins and small nucleolar RNAs are dysregulated in a Drosophila model for feline hypertrophic cardiomyopathy.G3 (Bethesda, Md.) · 2021Article
- The Genetic and Endoplasmic Reticulum-Mediated Molecular Mechanisms of Primary Open-Angle Glaucoma.International journal of molecular sciences · 2020Review
- Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects.Signal transduction and targeted therapy · 2020Review
- Accumulation of Asn450Tyr mutant myocilin in ER promotes apoptosis of human trabecular meshwork cells.Molecular vision · 2020Article
- Genetic Modifiers of Neurodegeneration in aGenetics · 2018Article
- Research progress on human genes involved in the pathogenesis of glaucoma (Review).Molecular medicine reports · 2018Review
- CRISPR-Cas9-based treatment of myocilin-associated glaucoma.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Article
- Genetic architecture of natural variation in visual senescence in Drosophila.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Candidate genetic modifiers of retinitis pigmentosa identified by exploiting natural variation in Drosophila.Human molecular genetics · 2016Article
- The pathogenic human Torsin A in Drosophila activates the unfolded protein response and increases susceptibility to oxidative stress.BMC genomics · 2015Article
- Structural basis for misfolding in myocilin-associated glaucoma.Human molecular genetics · 2015Article
- Olfactomedin proteins: central players in development and disease.Frontiers in cell and developmental biology · 2014Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGlaucoma is the world's second leading cause of bilateral blindness with progressive loss of vision due to retinal ganglion cell death. Myocilin has been associated with congenital glaucoma and 2-4% of primary open angle glaucoma (POAG) cases, but the pathogenic mechanisms remain largely unknown. Among several hypotheses, activation of the unfolded protein response (UPR) has emerged as a possible disease mechanism. METHODOLOGY / PRINCIPAL
findingsWe used a transgenic Drosophila model to analyze whole-genome transcriptional profiles in flies that express human wild-type or mutant MYOC in their eyes. The transgenic flies display ocular fluid discharge, reflecting ocular hypertension, and a progressive decline in their behavioral responses to light. Transcriptional analysis shows that genes associated with the UPR, ubiquitination, and proteolysis, as well as metabolism of reactive oxygen species and photoreceptor activity undergo altered transcriptional regulation. Following up on the results from these transcriptional analyses, we used immunoblots to demonstrate the formation of MYOC aggregates and showed that the formation of such aggregates leads to induction of the UPR, as evident from activation of the fluorescent UPR marker, xbp1-EGFP. CONCLUSIONS / SIGNIFICANCE: Our results show that aggregation of MYOC in the endoplasmic reticulum activates the UPR, an evolutionarily conserved stress pathway that culminates in apoptosis. We infer from the Drosophila model that MYOC-associated ocular hypertension in the human eye may result from aggregation of MYOC and induction of the UPR in trabecular meshwork cells. This process could occur at a late age with wild-type MYOC, but might be accelerated by MYOC mutants to account for juvenile onset glaucoma.
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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.