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Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice

Authors
 Ho K Lee  ;  Jinhong Park  ;  Bo-Rahm Kim  ;  Ikhyun Jun  ;  Tae-Im Kim  ;  Wan Namkung 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.22(8) : 3954, 2021-04 
Journal Title
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 
Issue Date
2021-04
MeSH
Animals ; Cystic Fibrosis Transmembrane Conductance Regulator / genetics* ; Disease Models, Animal ; Dry Eye Syndromes / drug therapy* ; Dry Eye Syndromes / genetics ; Dry Eye Syndromes / pathology ; Epithelial Cells / drug effects ; Gene Expression Regulation / drug effects ; Humans ; Interleukin-1beta / genetics ; Interleukin-8 / genetics ; Mice ; Quercetin / analogs & derivatives* ; Quercetin / pharmacology ; Tumor Necrosis Factor-alpha / genetics
Keywords
cystic fibrosis transmembrane conductance regulator ; dry eye ; isorhamnetin
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.
Files in This Item:
T202101658.pdf Download
DOI
10.3390/ijms22083954
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Tae-Im(김태임) ORCID logo https://orcid.org/0000-0001-6414-3842
Jun, Ik Hyun(전익현) ORCID logo https://orcid.org/0000-0002-2160-1679
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182965
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