ArticleNature communications2021
GLIS1 regulates trabecular meshwork function and intraocular pressure and is associated with glaucoma in humans.
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Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 34 citations in OpenAlex.
- Glis1 regulates metabolic programming by promoting H3K18 lactylation to alleviate neuronal senescence following spinal cord injury.Genes & diseases · 2027Article
- Schlemm's Canal Development and Implications for Glaucoma Treatment.Annual review of vision science · 2026Review
- Transcriptomic Profiling of High vs. Low Flow Regions of Mouse and Human Trabecular Meshwork.bioRxiv : the preprint server for biology · 2026Article
- Targeting Circadian Rhythm Disruption in Glaucoma: PTGDS Mediates Trabecular Meshwork Fibrosis and Is Therapeutically Targeted by Aprepitant.Translational vision science & technology · 2026Article
- Article
- AAV-DJ-Mediated MYOC Silencing as a Gene Therapy Approach for Myocilin-Associated Glaucoma.Investigative ophthalmology & visual science · 2026Article
- Tri-domain proteins 27 alleviates ischemia-reperfusion injury-induced acute kidney injury by promoting Gli-like transcription factor 1 expression via the inhibition of polycomb repressive complex 2 activity.Journal of cell communication and signaling · 2025Article
- Exploring diagnostic m6A regulators in primary open-angle glaucoma: insight from gene signature and possible mechanisms by which key genes function.BMC medical genomics · 2025Article
- Structural framework to address variant-gene relationship in primary open-angle glaucoma.Vision research · 2025Review
- Minimal phenotypes in transgenic mice with the human LOXL1/LOXL1-AS1 locus associated with exfoliation glaucoma.Vision research · 2024Article
- Tert-butyl hydroperoxide induces trabecular meshwork cells injury through ferroptotic cell death.Journal of cell communication and signaling · 2024Article
- Single-cell transcriptomic Atlas of aging macaque ocular outflow tissues.Protein & cell · 2024Article
- Serine to proline mutation at position 341 of MYOC impairs trabecular meshwork function by causing autophagy deregulation.Cell death discovery · 2024Article
- Glaucoma and dietary links: insights from high-salt intake, the Mediterranean diet, and specific nutrients.Frontiers in nutrition · 2024Review
- The mechanisms of natural products for eye disorders by targeting mitochondrial dysfunction.Frontiers in pharmacology · 2024Review
- The effect of ET1-CTGF mediated pathway on the accumulation of extracellular matrix in the trabecular meshwork and its contribution to the increase in IOP.International ophthalmology · 2023Article
- Human Pro370Leu Mutant Myocilin Induces the Phenotype of Open-Angle Glaucoma in Transgenic Mice.Cellular and molecular neurobiology · 2023Article
- Long non-coding RNA SNHG11 regulates the Wnt/β-catenin signaling pathway through rho/ROCK in trabecular meshwork cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- 10 Years of GWAS in intraocular pressure.Frontiers in genetics · 2023Review
- Physiological and pathological roles of Hic‑5 in several organs (Review).International journal of molecular medicine · 2022Review
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Authors and funding
22 authors at 10 institutions in 2 countries.
K Saidas Nair *Department of Ophthalmology and Department of Anatomy, School of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-5309-9727
Chitrangda Srivastava *Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Robert V Brown *Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Swanand KoliDepartment of Ophthalmology, School of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-4742-4439
Hélène ChoquetKaiser Permanente Northern California, Division of Research, Oakland, CA, USA.ORCID 0000-0001-9839-8667
Hong Soon KangImmunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Yien-Ming KuoDepartment of Ophthalmology, School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Sara A GrimmIntegrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.ORCID 0000-0003-3050-1909
Caleb SutherlandImmunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Alexandra BadeaCenter for In Vivo Microscopy, Department of Radiology, Duke University, Durham, NC, USA.ORCID 0000-0001-6621-4560
G Allan JohnsonCenter for In Vivo Microscopy, Department of Radiology, Duke University, Durham, NC, USA.
Yin ZhaoDepartment of Ophthalmology, School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Jie YinKaiser Permanente Northern California, Division of Research, Oakland, CA, USA.
Kyoko OkamotoImmunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Graham ClarkThe Jackson Laboratory, Bar Harbor, ME, USA.
Terete BorrásDepartment of Ophthalmology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Gulab ZodeDepartment of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX, USA.ORCID 0000-0002-7823-2595
Krishnakumar KizhatilThe Jackson Laboratory, Bar Harbor, ME, USA.ORCID 0000-0003-3755-6101
Subhabrata ChakrabartiBrien Holden Eye Research Centre, L. V. Prasad Eye Institute, Hyderabad, India.ORCID 0000-0003-3717-4963
Simon W M JohnThe Jackson Laboratory, Bar Harbor, ME, USA.
Eric JorgensonRegeneron Pharmaceuticals, Inc, Tarrytown, NY, USA.ORCID 0000-0002-5829-8191
Anton M JettenImmunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. jetten@nih.gov.ORCID 0000-0003-0954-4445
National Institutes of Health · USUniversity of California, San Francisco · USDuke University · USJackson Laboratory · USKaiser Permanente · USHoward Hughes Medical Institute · USL V Prasad Eye Institute · INRegeneron (United States) · USUniversity of North Carolina at Chapel Hill · USUniversity of North Texas · US
Funding
Mechanism Of Action And Functions Of The Gli-related Proteins Glis 1-3ZIAES100485 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI JETTEN, ANTON M · 2009 to 2025
$35.9MRapid-Prototyping and Design CoreP30EY002162 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LAKKARAJU, APARNA · 1985 to 2024
$16.8MFactors Determining Intraocular Pressure and Glaucoma SusceptibilityR01EY011721 · NEI · JACKSON LABORATORY · PI JOHN, SIMON W · 2002 to 2018
$12.4MCrosstalk Between Unfolded Protein Response and Autophagy for the Treatment of GlaucomaR01EY026177 · NEI · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI ZODE, GULAB · 2016 to 2025
$3.8MMechanism Of Action And Functions Of The Gli-related Proteins Glis 1-3Z01ES100485 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI JETTEN, ANTON M · 2002 to 2008
$2.3MDetermining How Lymphatic Molecules Control Conventional OutflowR01EY028175 · NEI · JACKSON LABORATORY · PI KIZHATIL, KRISHNAKUMAR · 2017 to 2021
$2.3MDetermining Molecular and Cellular Mechanisms of GlaucomaR01EY022891 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NAIR, KAYARAT SAIDAS · 2013 to 2017
$2.0MTargeting calcification/ stiffness in glaucoma with Matrix GlaR01EY026220 · NEI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MEI, HUA · 2016 to 2020
$1.9MGenetic Etiology of Abdominal Hernia SusceptibilityR01DK116738 · NIDDK · KAISER FOUNDATION RESEARCH INSTITUTE · PI AHITUV, NADAV, CHOQUET, HELENE · 2018 to 2020
$1.8MThe Role of Refractive Error in the Etiology of GlaucomaR01EY027004 · NEI · KAISER FOUNDATION RESEARCH INSTITUTE · PI CHOQUET, HELENE · 2017 to 2020
$1.6MFACTORS DETERMINING INTRAOCULAR PRESSURER29EY011721 · NEI · JACKSON LABORATORY · PI JOHN, SIMON W · 1997 to 2001
$227kHoward Hughes Medical InstituteIntramural NIH HHS Z01 ES100485NEI NIH HHS P30 EY002162NEI NIH HHS R01 EY011721NEI NIH HHS R01 EY022891NEI NIH HHS R01 EY026177NEI NIH HHS R01 EY026220NEI NIH HHS R01 EY027004NEI NIH HHS R01 EY028175NEI NIH HHS R29 EY011721NIDDK NIH HHS R01 DK116738
Abstract
Chronically elevated intraocular pressure (IOP) is the major risk factor of primary open-angle glaucoma, a leading cause of blindness. Dysfunction of the trabecular meshwork (TM), which controls the outflow of aqueous humor (AqH) from the anterior chamber, is the major cause of elevated IOP. Here, we demonstrate that mice deficient in the Krüppel-like zinc finger transcriptional factor GLI-similar-1 (GLIS1) develop chronically elevated IOP. Magnetic resonance imaging and histopathological analysis reveal that deficiency in GLIS1 expression induces progressive degeneration of the TM, leading to inefficient AqH drainage from the anterior chamber and elevated IOP. Transcriptome and cistrome analyses identified several glaucoma- and extracellular matrix-associated genes as direct transcriptional targets of GLIS1. We also identified a significant association between GLIS1 variant rs941125 and glaucoma in humans (P = 4.73 × 10
Indexed as
Disease Models, AnimalAnimalsAqueous HumorChromatin Immunoprecipitation SequencingDNA-Binding ProteinsGene Expression ProfilingGene Expression RegulationGlaucomaHEK293 CellsHumansIntraocular PressureMiceMice, Inbred C57BLMice, KnockoutRNA-SeqTrabecular MeshworkDNA-Binding ProteinsGlis1 protein, mouseTranscription Factors
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