ArticleLaboratory investigation; a journal of technical methods and pathology2019
Sensory nerve supports epithelial stem cell function in healing of corneal epithelium in mice: the role of trigeminal nerve transient receptor potential vanilloid 4.
Article in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- Corneal macrophages and limbal stem cells: emerging roles in ocular surface regeneration.Annals of medicine · 2026Review
- Topohistological alignments of ocular/penile organs.Anatomical science international · 2026Review
- Management of Stage 1 Neurotrophic Keratopathy with Shelf-Stable, Cryopreserved Amniotic Membrane: A Retrospective Study.Clinical ophthalmology (Auckland, N.Z.) · 2026Article
- Transient receptor potential vanilloid 4 modulates substrate stiffness mechanosensing and transcellular pore formation in human Schlemm's canal cells.Acta biomaterialia · 2025Article
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- Developing stem cells for corneal disease: recent developments and future perspectives.Regenerative medicine · 2025Review
- TRPV4 modulates substrate stiffness mechanosensing and transcellular pore formation in human Schlemm's canal cells.bioRxiv : the preprint server for biology · 2025Article
- Clodronate liposome treatment contributes to the nerve regeneration in corneal nerve involvement of diabetic mice.Experimental animals · 2025Article
- Shelf-Stable, Cryopreserved Amniotic Membrane for the Management of Ocular Surface Disease: A Retrospective Assessment.Clinical optometry · 2025Article
- Topical application of calcitonin gene-related peptide as a regenerative, antifibrotic, and immunomodulatory therapy for corneal injury.Communications biology · 2024Article
- A nerve-goblet cell association promotes allergic conjunctivitis through rapid antigen passage.JCI insight · 2023Article
- Corneal Neurotization: Preoperative Patient Workup and Surgical Decision-making.Plastic and reconstructive surgery. Global open · 2023Article
- Topical application of calcitonin gene-related peptide as a regenerative, antifibrotic, and immunomodulatory therapy for corneal injury.Research square · 2023Article
- A Method for Real-Time Assessment of Mitochondrial Respiration Using Murine Corneal Biopsy.Investigative ophthalmology & visual science · 2023Article
- Culture of Primary Neurons from Dissociated and Cryopreserved Mouse Trigeminal Ganglion.Tissue engineering. Part C, Methods · 2023Article
- Effect of TRPM8 Functional Loss on Corneal Epithelial Wound Healing in Mice.Investigative ophthalmology & visual science · 2023Article
- Association of Treatment Duration and Clinical Outcomes in Dry Eye Treatment with Sutureless Cryopreserved Amniotic Membrane.Clinical ophthalmology (Auckland, N.Z.) · 2023Article
- Effect of Polydeoxyribonucleotide (PDRN) Treatment on Corneal Wound Healing in Zebrafish (International journal of molecular sciences · 2022Article
- Transient Receptor Potential Channels: Important Players in Ocular Pain and Dry Eye Disease.Pharmaceutics · 2022Review
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
Abstract
In order to understand the pathobiology of neurotrophic keratopathy, we established a mouse model by coagulating the first branch of the trigeminal nerve (V1 nerve). In our model, the sensory nerve in the central cornea disappeared and remaining fibers were sparse in the peripheral limbal region. Impaired corneal epithelial healing in the mouse model was associated with suppression of both cell proliferation and expression of stem cell markers in peripheral/limbal epithelium as well as a reduction of transient receptor potential vanilloid 4 (TRPV4) expression in tissue. TRPV4 gene knockout also suppressed epithelial repair in mouse cornea, although it did not seem to directly modulate migration of epithelium. In a co-culture experiment, TRPV4-introduced KO trigeminal ganglion upregulated nerve growth factor (NGF) in cultured corneal epithelial cells, but ganglion with a control vector did not. TRPV4 gene introduction into a damaged V1 nerve rescues the impairment of epithelial healing in association with partial recovery of the stem/progenitor cell markers and upregulation of cell proliferation and of NGF expression in the peripheral/limbal epithelium. Gene transfer of TRPV4 did not accelerate the regeneration of nerve fibers. Sensory nerve TRPV4 is critical to maintain stemness of peripheral/limbal basal cells, and is one of the major mechanisms of homeostasis maintenance of corneal epithelium.
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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.