Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/93493
Title: | Mechanistic effects of Baicalein on aqueous humor drainage and intraocular pressure | Authors: | Li, H Shan, SW Stamer, WD Li, K Chan, HH Civan, MM To, C Lam, TC Do, C |
Issue Date: | Jul-2022 | Source: | International journal of molecular sciences, July 2022, v. 23, no. 13, 7372 | Abstract: | Elevated intraocular pressure (IOP) is a major risk factor for glaucoma that results from impeded fluid drainage. The increase in outflow resistance is caused by trabecular meshwork (TM) cell dysfunction and excessive extracellular matrix (ECM) deposition. Baicalein (Ba) is a natural flavonoid and has been shown to regulate cell contraction, fluid secretion, and ECM remodeling in various cell types, suggesting the potential significance of regulating outflow resistance and IOP. We demonstrated that Ba significantly lowered the IOP by about 5 mmHg in living mice. Consistent with that, Ba increased the outflow facility by up to 90% in enucleated mouse eyes. The effects of Ba on cell volume regulation and contractility were examined in primary human TM (hTM) cells. We found that Ba (1–100 µM) had no effect on cell volume under iso-osmotic conditions but inhibited the regulatory volume decrease (RVD) by up to 70% under hypotonic challenge. In addition, Ba relaxed hTM cells via reduced myosin light chain (MLC) phosphorylation. Using iTRAQ-based quantitative proteomics, 47 proteins were significantly regulated in hTM cells after a 3-h Ba treatment. Ba significantly increased the expression of cathepsin B by 1.51-fold and downregulated the expression of D-dopachrome decarboxylase and pre-B-cell leukemia transcription factor-interacting protein 1 with a fold-change of 0.58 and 0.40, respectively. We suggest that a Ba-mediated increase in outflow facility is triggered by cell relaxation via MLC phosphorylation along with inhibiting RVD in hTM cells. The Ba-mediated changes in protein expression support the notion of altered ECM homeostasis, potentially contributing to a reduction of outflow resistance and thereby IOP. | Keywords: | Baicalein Intraocular pressure Outflow facility Trabecular meshwork Cell contractility Regulatory volume decrease Extracellular matrix Proteomics Glaucoma |
Publisher: | Molecular Diversity Preservation International (MDPI) | Journal: | International journal of molecular sciences | ISSN: | 1661-6596 | EISSN: | 1422-0067 | DOI: | 10.3390/ijms23137372 | Rights: | © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). The following publication Li, H. L., Shan, S. W., Stamer, W. D., Li, K. K., Chan, H. H. L., Civan, M. M., ... & Do, C. W. (2022). Mechanistic Effects of Baicalein on Aqueous Humor Drainage and Intraocular Pressure. International Journal of Molecular Sciences, 23(13), 7372 is available at https://doi.org/10.3390/ijms23137372 |
Appears in Collections: | Journal/Magazine Article |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
ijms-23-07372.pdf | 1.27 MB | Adobe PDF | View/Open |
Page views
65
Last Week
2
2
Last month
Citations as of May 5, 2024
Downloads
35
Citations as of May 5, 2024
SCOPUSTM
Citations
3
Citations as of Apr 19, 2024
WEB OF SCIENCETM
Citations
4
Citations as of May 2, 2024
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.