ArticlePloS one2018
KCa3.1 ion channel: A novel therapeutic target for corneal fibrosis.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 44 citations in OpenAlex.
- Myogenic Differentiation (MyoD) Gene Expression in Cornea and Role in Corneal Myofibroblast Dedifferentiation.Investigative ophthalmology & visual science · 2026Article
- Alterations in Mitochondrial DNA in Corneal Fibroblast and Myofibroblast Post Injury.Investigative ophthalmology & visual science · 2026Article
- Long-Term Tolerability and Safety of AAV5-Id3 Gene Therapy to Eyes.Translational vision science & technology · 2026Article
- The cornea-trigeminal axis: potassium channels as master regulators of ocular surface homeostasis and sensory transduction.Frontiers in cell and developmental biology · 2026Review
- Genetic silencing of KChannels (Austin, Tex.) · 2025Article
- Epigenetic Reprogramming Via Sodium Butyrate Induces Corneal Myofibroblast Dedifferentiation In Vitro and Inhibits Fibrosis In Vivo.Investigative ophthalmology & visual science · 2025Article
- Open-Field Blast Injury Disrupts Corneal Gene Expression Linked to Ion Transport, Sensory Perception, and Neural Signaling.Investigative ophthalmology & visual science · 2025Article
- The role and mechanism of vascular wall cell ion channels in vascular fibrosis remodeling.Channels (Austin, Tex.) · 2024Review
- Blast injury: Impact to the cornea.Experimental eye research · 2024Review
- The key mediator of diabetic kidney disease: Potassium channel dysfunction.Genes & diseases · 2024Review
- Regenerative Therapy for Corneal Scarring Disorders.Biomedicines · 2024Review
- KCNK5 Regulating Potassium Efflux and Inducing Pyroptosis in Corneal Epithelial Cells Through TNFSF10-Mediated Autophagy in Dry Eye.Investigative ophthalmology & visual science · 2024Article
- Analysis of Smad3 in the modulation of stromal extracellular matrix proteins in corneal scarring after alkali injury.Molecular vision · 2024Article
- Toxicological effects of ocular acrolein exposure to eyelids in rabbits in vivo.Experimental eye research · 2023Article
- Corneal stromal repair and regeneration.Progress in retinal and eye research · 2022Review
- Review
- Corneal fibrosis abrogation by a localized AAV-mediated inhibitor of differentiation 3 (Id3) gene therapy in rabbit eyes in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of CaLife (Basel, Switzerland) · 2022Article
- Evaluation of a novel combination of TRAM-34 and ascorbic acid for the treatment of corneal fibrosis in vivo.PloS one · 2022Article
- Synthesis and biological evaluation of PET tracers designed for imaging of calcium activated potassium channel 3.1 (KRSC advances · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Vision impairment from corneal fibrosis is a common consequence of irregular corneal wound healing after injury. Intermediate-conductance calmodulin/calcium-activated K+ channels 3.1 (KCa3.1) play an important role in cell cycle progression and cellular proliferation. Proliferation and differentiation of corneal fibroblasts to myofibroblasts can lead to corneal fibrosis after injury. KCa3.1 has been shown in many non-ocular tissues to promote fibrosis, but its role in corneal fibrosis is still unknown. In this study, we characterized the expression KCa3.1 in the human cornea and its role in corneal wound healing in vivo using a KCa3.1 knockout (KCa3.1-/-) mouse model. Additionally, we tested the hypothesis that blockade of KCa3.1 by a selective KCa3.1 inhibitor, TRAM-34, could augment a novel interventional approach for controlling corneal fibrosis in our established in vitro model of corneal fibrosis. The expression of KCa3.1 gene and protein was analyzed in human and murine corneas. Primary human corneal fibroblast (HCF) cultures were used to examine the potential of TRAM-34 in treating corneal fibrosis by measuring levels of pro-fibrotic genes, proteins, and cellular migration using real-time quantitative qPCR, Western blotting, and scratch assay, respectively. Cytotoxicity of TRAM-34 was tested with trypan blue assay, and pro-fibrotic marker expression was tested in KCa3.1-/-. Expression of KCa3.1 mRNA and protein was detected in all three layers of the human cornea. The KCa3.1-/- mice demonstrated significantly reduced corneal fibrosis and expression of pro-fibrotic marker genes such as collagen I and α-smooth muscle actin (α-SMA), suggesting that KCa3.1 plays an important role corneal wound healing in vivo. Pharmacological treatment with TRAM-34 significantly attenuated corneal fibrosis in vitro, as demonstrated in HCFs by the inhibition TGFβ-mediated transcription of pro-fibrotic collagen I mRNA and α-SMA mRNA and protein expression (p<0.001). No evidence of cytotoxicity was observed. Our study suggests that KCa3.1 regulates corneal wound healing and that blockade of KCa3.1 by TRAM-34 offers a potential therapeutic strategy for developing therapies to cure corneal fibrosis in vivo.
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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.