Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice.
Ho K LeeJinhong ParkBo-Rahm KimIkhyun JunTae-Im KimWan NamkungPublished in: International journal of molecular sciences (2021)
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.
Keyphrases
- cystic fibrosis
- pseudomonas aeruginosa
- lung function
- mouse model
- wild type
- rheumatoid arthritis
- stem cells
- chronic obstructive pulmonary disease
- binding protein
- immune response
- high glucose
- mesenchymal stem cells
- electronic health record
- bone marrow
- endothelial cells
- climate change
- long non coding rna
- big data
- machine learning
- toll like receptor
- insulin resistance
- reactive oxygen species