Related Experiment Video
Updated: Nov 7, 2025
A Chronic Autoimmune Dry Eye Rat Model with Increase in Effector Memory T Cells in Eyeball Tissue
Published on: June 7, 2017
Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice
Ho K Lee1,2, Jinhong Park1, Bo-Rahm Kim3
1College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea.
Abstract:
Dry eye disease is one of the most common diseases, with increasing prevalence in many countries, but treatment options are limited. Cystic fibrosis transmembrane conductance regulator (CFTR) is a major ion channel that facilitates fluid secretion in ocular surface epithelium and is a potential target of therapeutic agent for the treatment of dry eye disease. In this study, we performed a cell-based, high-throughput screening for the identification of novel natural products that activate CFTR and restore the aqueous deficiency in dry eye. Screening of 1000 natural products revealed isorhamnetin, a flavonol aglycone, as a novel CFTR activator. Electrophysiological studies showed that isorhamnetin significantly increased CFTR chloride current, both wild type and ∆F508-CFTR. Isorhamnetin did not alter intracellular cAMP levels and the activity of other ion channels, including ANO1, ENaC, and hERG. Notably, application of isorhamnetin on mouse ocular surface induced CFTR activation and increased tear volume. In addition, isorhamnetin significantly reduced ocular surface damage and expression of interleukin (IL)-1β, IL-8, and tumor necrosis factor (TNF)-α in an experimental mouse model of dry eye. These data suggest that isorhamnetin may be used to treat dry eye disease.
Insights
Isorhamnetin, a natural compound, activates the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. This discovery offers a potential new treatment for dry eye disease by restoring ocular surface fluid secretion.
Area of Science:
- Ophthalmology
- Pharmacology
- Molecular Biology
Background:
- Dry eye disease is a prevalent condition with limited therapeutic options.
- The cystic fibrosis transmembrane conductance regulator (CFTR) is crucial for ocular surface fluid secretion and a potential therapeutic target.
- Novel therapeutic strategies are needed to address the increasing prevalence of dry eye disease.
Purpose of the Study:
- To identify novel natural products that activate CFTR for dry eye disease treatment.
- To investigate the potential of isorhamnetin as a CFTR activator and therapeutic agent for dry eye.
Main Methods:
- Conducted a high-throughput screening of 1000 natural products to identify CFTR activators.
- Utilized electrophysiological studies to assess isorhamnetin's effect on CFTR activity (wild type and ∆F508-CFTR).
- Evaluated isorhamnetin's efficacy in a mouse model of dry eye, measuring tear volume, ocular surface damage, and inflammatory markers.
Main Results:
- Identified isorhamnetin, a flavonol aglycone, as a novel CFTR activator.
- Isorhamnetin significantly increased CFTR chloride current without affecting other ion channels or cAMP levels.
- In vivo studies demonstrated that isorhamnetin increased tear volume, reduced ocular surface damage, and decreased inflammation in a dry eye model.
Conclusions:
- Isorhamnetin effectively activates CFTR and restores aqueous deficiency in dry eye.
- Isorhamnetin exhibits therapeutic potential for treating dry eye disease.
- This study highlights isorhamnetin as a promising natural compound for dry eye management.
