ArticleProceedings of the National Academy of Sciences of the United States of America2014
Primary cilia signaling mediates intraocular pressure sensation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 153 citations in OpenAlex.
- TRPV4 regulates intraocular pressure through trabecular meshwork contractility and fibrosis.Channels (Austin, Tex.) · 2026Review
- CRISPR and Gene Augmentation Rescue Trabecular Meshwork Dysfunction in iPSC Models of Lowe Syndrome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Primary Cilia of Astrocytes in the Retina in Development and Disease.Investigative ophthalmology & visual science · 2026Article
- Transcriptomic Atlas of Human Trabecular Meshwork Uncovers the Cellular Landscape and Provides Insights into Glaucoma Pathophysiology.Research square · 2026Article
- The TRPV4-YAP axis mediates cytoskeletal and extracellular matrix remodeling in trabecular meshwork cells as a novel glaucoma mechanism.Scientific reports · 2025Article
- Transient receptor potential vanilloid 4 modulates substrate stiffness mechanosensing and transcellular pore formation in human Schlemm's canal cells.Acta biomaterialia · 2025Article
- Primary Cilia in Hepatic Biliary Hyperplasia: Implications for Liver Diseases.Seminars in liver disease · 2025Review
- Lens Proteomics Provide Novel Clues for Cataractogenesis: Original Investigation and a Broad Literature Survey.Journal of clinical medicine · 2025Article
- TRPV4 controls circadian and pathological ocular hypertension.The Journal of physiology · 2025Article
- Methods for Mitochondrial DNA Damage and Depletion in Immortalized Trabecular Meshwork Cells.International journal of molecular sciences · 2025Article
- TRPV4 activation by TGFβ2 enhances cellular contractility and drives ocular hypertension.eLife · 2025Article
- Biomechanical properties of the trabecular meshwork in intraocular pressure regulation: a review.International ophthalmology · 2025Review
- TRPV4 modulates substrate stiffness mechanosensing and transcellular pore formation in human Schlemm's canal cells.bioRxiv : the preprint server for biology · 2025Article
- Class I PI3Ks activate stretch-induced autophagy in trabecular meshwork cells.Cellular and molecular life sciences : CMLS · 2025Article
- Mechanobiology in the eye.npj biological physics and mechanics · 2025Review
- Role of Primary Cilia in the Eye.Advances in experimental medicine and biology · 2025Review
- Resting trabecular meshwork cells experience constitutive cation influx.Vision research · 2024Article
- The relationship between intraocular pressure and glaucoma: An evolving concept.Progress in retinal and eye research · 2024Review
- Mechanosensitive ion channels in glaucoma pathophysiology.Vision research · 2024Review
- Mechanism of barotaxis in marine zooplankton.eLife · 2024Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 9 institutions in 2 countries.
Funding
Abstract
Lowe syndrome is a rare X-linked congenital disease that presents with congenital cataracts and glaucoma, as well as renal and cerebral dysfunction. OCRL, an inositol polyphosphate 5-phosphatase, is mutated in Lowe syndrome. We previously showed that OCRL is involved in vesicular trafficking to the primary cilium. Primary cilia are sensory organelles on the surface of eukaryotic cells that mediate mechanotransduction in the kidney, brain, and bone. However, their potential role in the trabecular meshwork (TM) in the eye, which regulates intraocular pressure, is unknown. Here, we show that TM cells, which are defective in glaucoma, have primary cilia that are critical for response to pressure changes. Primary cilia in TM cells shorten in response to fluid flow and elevated hydrostatic pressure, and promote increased transcription of TNF-α, TGF-β, and GLI1 genes. Furthermore, OCRL is found to be required for primary cilia to respond to pressure stimulation. The interaction of OCRL with transient receptor potential vanilloid 4 (TRPV4), a ciliary mechanosensory channel, suggests that OCRL may act through regulation of this channel. A novel disease-causing OCRL allele prevents TRPV4-mediated calcium signaling. In addition, TRPV4 agonist GSK 1016790A treatment reduced intraocular pressure in mice; TRPV4 knockout animals exhibited elevated intraocular pressure and shortened cilia. Thus, mechanotransduction by primary cilia in TM cells is implicated in how the eye senses pressure changes and highlights OCRL and TRPV4 as attractive therapeutic targets for the treatment of glaucoma. Implications of OCRL and TRPV4 in primary cilia function may also shed light on mechanosensation in other organ systems.
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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.