ArticleProceedings of the National Academy of Sciences of the United States of America2019
Increased stiffness and flow resistance of the inner wall of Schlemm's canal in glaucomatous human eyes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.
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Who cites it
90 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- Advances in glaucoma biomechanics from 2000 to 2024: a bibliometric study and visualization analysis.Frontiers in neuroscience · 2025Pooled it
- Segmental flow responses in glaucomatous trabecular meshwork cells.Biomaterials advances · 2026Article
- Article
- Comprehensive, High-Spatiotemporal-Resolution Intravital Two-Photon Imaging of the Mouse Conventional Outflow Pathway: Green Intravital Imaging.Investigative ophthalmology & visual science · 2026Article
- Microtubule stability modulates Schlemm's canal cell mechanobiology and outflow facility in glaucoma.bioRxiv : the preprint server for biology · 2026Article
- Segmental Mechanobiology of Normal and Glaucomatous Human Trabecular Meshwork Cells.ACS measurement science au · 2026Article
- Flow-dependent traction in high- and low-flow normal trabecular meshwork cells.Acta biomaterialia · 2026Article
- Endothelial cell stiffness and type drive the formation of biomechanically induced transcellular pores.Cell reports · 2026Article
- Early success and safety of three minimally invasive glaucoma surgery techniques combined with cataract surgery in glaucoma patients.International ophthalmology · 2025Observational
- Mechano- and Glucocorticoid-Sensitive TREK-1 Channels Regulate Conventional Outflow and Intraocular Pressure.Investigative ophthalmology & visual science · 2025Article
- Review
- Transient receptor potential vanilloid 4 modulates substrate stiffness mechanosensing and transcellular pore formation in human Schlemm's canal cells.Acta biomaterialia · 2025Article
- Substrate stiffness and pressure alter retinal Müller glia response and extracellular matrix production.Biomaterials and biosystems · 2025Article
- Lipids and lipid regulators in intraocular pressure homeostasis.Current opinion in pharmacology · 2025Review
- TRPV4 modulates substrate stiffness mechanosensing and transcellular pore formation in human Schlemm's canal cells.bioRxiv : the preprint server for biology · 2025Article
- Caveolae: Metabolic Platforms at the Crossroads of Health and Disease.International journal of molecular sciences · 2025Review
- Astrocytes in the mouse brain respond bilaterally to unilateral retinal neurodegeneration.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Characterization, Enrichment, and Computational Modeling of Cross-Linked Actin Networks in Transformed Trabecular Meshwork Cells.Investigative ophthalmology & visual science · 2025Article
- Effect of intraocular pressure on crystalline lens oscillations: a computational study using porcine eye model.PloS one · 2025Article
- Mechanobiology in the eye.npj biological physics and mechanics · 2025Review
30 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The cause of the elevated outflow resistance and consequent ocular hypertension characteristic of glaucoma is unknown. To investigate possible causes for this flow resistance, we used atomic force microscopy (AFM) with 10-µm spherical tips to probe the stiffness of the inner wall of Schlemm's canal as a function of distance from the tissue surface in normal and glaucomatous postmortem human eyes, and 1-µm spherical AFM tips to probe the region immediately below the tissue surface. To localize flow resistance, perfusion and imaging methods were used to characterize the pressure drop in the immediate vicinity of the inner wall using giant vacuoles that form in Schlemm's canal cells as micropressure sensors. Tissue stiffness increased with increasing AFM indentation depth. Tissues from glaucomatous eyes were stiffer compared with normal eyes, with greatly increased stiffness residing within ∼1 µm of the inner-wall surface. Giant vacuole size and density were similar in normal and glaucomatous eyes despite lower flow rate through the latter due to their higher flow resistance. This implied that the elevated flow resistance found in the glaucomatous eyes was localized to the same region as the increased tissue stiffness. Our findings implicate pathological changes to biophysical characteristics of Schlemm's canal endothelia and/or their immediate underlying extracellular matrix as cause for ocular hypertension in 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.