ArticleProceedings of the National Academy of Sciences of the United States of America2020
Molecular taxonomy of human ocular outflow tissues defined by single-cell transcriptomics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
- Genome-wide analysis of genetic pleiotropy and causal genes across three age-related ocular disorders.Human genetics · 2023Pooled it
- Tie2 Activation via VE-PTP Inhibition With Razuprotafib as an Adjunct to Latanoprost in Patients With Open Angle Glaucoma or Ocular Hypertension.Translational vision science & technology · 2022Trial
- A Small Molecule Inhibitor of VE-PTP Activates Tie2 in Schlemm's Canal Increasing Outflow Facility and Reducing Intraocular Pressure.Investigative ophthalmology & visual science · 2020Trial
- Schlemm's Canal Development and Implications for Glaucoma Treatment.Annual review of vision science · 2026Review
- A Human Pharmacogenomics Approach Provides Insight Into the Pathogenesis and Pathophysiology of Steroid-Induced Ocular Hypertension.Ophthalmology science · 2026Article
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- An Integrated muti-omics cell atlas of the human trabecular meshwork and ciliary body.bioRxiv : the preprint server for biology · 2026Article
- Transcriptomic Atlas of Human Trabecular Meshwork Uncovers the Cellular Landscape and Provides Insights into Glaucoma Pathophysiology.Research square · 2026Article
- Targeting Rap1-YAP1 mechanosignaling for ameliorating acute IOP elevation-induced trabecular meshwork dysfunction.iScience · 2026Article
- Bioengineered 3D Human Trabecular Meshwork Models for Outflow Physiology and Glaucoma Research.Bioengineering (Basel, Switzerland) · 2026Review
- Article
- Experimental models to study oxidative stress in glaucoma: integratingFrontiers in pharmacology · 2026Review
- Applications of single-cell transcriptomics in glaucoma research: from the aqueous humor outflow pathway to retinal ganglion cell neurodegeneration.Frontiers in physiology · 2026Review
- iPSC-derived ITGA6-positive cells restore aqueous humor outflow in glaucoma eyes.Nature communications · 2025Article
- Piezo1 Activates an Autocrine Angiopoietin-2-Integrin Signaling Loop in Schlemm's Canal to Regulate Intraocular Pressure.bioRxiv : the preprint server for biology · 2025Article
- Single-cell profiling of trabecular meshwork identifies mitochondrial dysfunction in a glaucoma model that is protected by vitamin B3 treatment.bioRxiv : the preprint server for biology · 2025Article
- The Advance of Single-Cell RNA Sequencing Applications in Ocular Physiology and Disease Research.Biomolecules · 2025Review
- Transcriptome Profiling of Trabecular Meshwork Progenitor Cells.Stem cell reviews and reports · 2025Article
- Hsa-MiR-483 -3p regulates the extracellular matrix proteins via TGFβ2/SMAD4 signaling in the glucocorticoid-responsive human trabecular meshwork cells.Cell and tissue research · 2025Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
The conventional outflow pathway is a complex tissue responsible for maintaining intraocular pressure (IOP) homeostasis. The coordinated effort of multiple cells with differing responsibilities ensures healthy outflow function and IOP maintenance. Dysfunction of one or more resident cell types results in ocular hypertension and risk for glaucoma, a leading cause of blindness. In this study, single-cell RNA sequencing was performed to generate a comprehensive cell atlas of human conventional outflow tissues. We obtained expression profiles of 17,757 genes from 8,758 cells from eight eyes of human donors representing the outflow cell transcriptome. Upon clustering analysis, 12 distinct cell types were identified, and region-specific expression of candidate genes was mapped in human tissues. Significantly, we identified two distinct expression patterns (myofibroblast- and fibroblast-like) from cells located in the trabecular meshwork (TM), the primary structural component of the conventional outflow pathway. We also located Schwann cell and macrophage signatures in the TM. The second primary component structure, Schlemm's canal, displayed a unique combination of lymphatic/blood vascular gene expression. Other expression clusters corresponded to cells from neighboring tissues, predominantly in the ciliary muscle/scleral spur, which together correspond to the uveoscleral outflow pathway. Importantly, the utility of our atlas was demonstrated by mapping glaucoma-relevant genes to outflow cell clusters. Our study provides a comprehensive molecular and cellular classification of conventional and unconventional outflow pathway structures responsible for IOP homeostasis.
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