ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
Small-molecule CFTR activators increase tear secretion and prevent experimental dry eye disease.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The trial behind it
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Model of ocular surface ion and water transport predicts efficacy of dry eye therapeutics.The Journal of general physiology · 2026Article
- Epithelial plasma membrane transporters as drug targets.Physiological reviews · 2026Review
- Lysophosphatidic acid receptor 3 (LPAR3) regulates ocular surface chloride transport via calcium signaling.Experimental eye research · 2025Article
- Calcium-sensing receptor (CaSR) modulates ocular surface chloride transport and its inhibition promotes ocular surface hydration.The ocular surface · 2024Article
- Ocular Changes in Cystic Fibrosis: A Review.International journal of molecular sciences · 2024Review
- Understanding CFTR Functionality: A Comprehensive Review of Tests and Modulator Therapy in Cystic Fibrosis.Cell biochemistry and biophysics · 2024Review
- Overview of CFTR activators and their recent studies for dry eye disease: a review.RSC medicinal chemistry · 2023Review
- Animal Models in Eye Research: Focus on Corneal Pathologies.International journal of molecular sciences · 2023Review
- Ion channels in dry eye disease.Indian journal of ophthalmology · 2023Review
- Synthetic Strategies for Improving Solubility: Optimization of Novel Pyrazolo[1,5-Journal of medicinal chemistry · 2023Article
- Expression of CFTR, a hallmark gene of ionocytes, is downregulated in salivary glands of Sjögren's syndrome patients.Arthritis research & therapy · 2022Article
- Ocular Surface Ion Transport and Dry Eye Disease.Current ophthalmology reports · 2022Article
- Conjunctival Fluid Secretion Impairment via CaCC-CFTR Dysfunction Is the Key Mechanism in Environmental Dry Eye.International journal of molecular sciences · 2022Article
- Novel CFTR Activator Cact-3 Ameliorates Ocular Surface Dysfunctions in Scopolamine-Induced Dry Eye Mice.International journal of molecular sciences · 2022Article
- Ocular Surface Ion-Channels Are Closely Related to Dry Eye: Key Research Focus on Innovative Drugs for Dry Eye.Frontiers in medicine · 2022Review
- Chloride transport modulators as drug candidates.American journal of physiology. Cell physiology · 2021Review
- Advantages and Disadvantages of Using Magnetic Nanoparticles for the Treatment of Complicated Ocular Disorders.Pharmaceutics · 2021Review
- Ocular Surface Potential Difference Measured in Human Subjects to Study Ocular Surface Ion Transport.Translational vision science & technology · 2020Article
- Nanomolar Potency Aminophenyltriazine CFTR Activator Reverses Corneal Epithelial Injury in a Mouse Model of Dry Eye.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2020Article
- Cellular mechanism for herbal medicine Junchoto to facilitate intestinal ClJournal of natural medicines · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Dry eye disorders, including Sjögren's syndrome, constitute a common problem in the aging population, with limited effective therapeutic options available. The cAMP-activated Cl(-) channel cystic fibrosis transmembrane conductance regulator (CFTR) is a major prosecretory channel at the ocular surface. We investigated whether compounds that target CFTR can correct the abnormal tear film in dry eye. Small-molecule activators of human wild-type CFTR identified by high-throughput screening were evaluated in cell culture and in vivo assays, to select compounds that stimulate Cl(-)-driven fluid secretion across the ocular surface in mice. An aminophenyl-1,3,5-triazine, CFTRact-K089, fully activated CFTR in cell cultures with EC50 ∼250 nM and produced an ∼8.5 mV hyperpolarization in ocular surface potential difference. When delivered topically, CFTRact-K089 doubled basal tear volume for 4 h and had no effect in CF mice. CFTRact-K089 showed sustained tear film bioavailability without detectable systemic absorption. In a mouse model of aqueous-deficient dry eye produced by lacrimal ablation, topical administration of 0.1 nmol CFTRact-K089 3 times daily restored tear volume to basal levels, preventing corneal epithelial disruption when initiated at the time of surgery and reversing it when started after development of dry eye. Our results support the potential utility of CFTR-targeted activators as a novel prosecretory treatment for dry eye.-Flores, A. M., Casey, S. D., Felix, C. M., Phuan, P. W., Verkman, A. S., Levin, M. H. Small-molecule CFTR activators increase tear secretion and prevent experimental dry eye disease.
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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.