Mechanistic Effects of Baicalein on Aqueous Humor Drainage and Intraocular Pressure

Hoi-lam Li, Sze Wan Sze-wan Shan, W. Daniel Daniel Stamer, King-kit Li, Henry Ho-lung Chan, Mortimer M. Civan, Chi-ho To, Thomas Chuen Lam, Chi-wai Do (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

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.
Original languageEnglish
Article number7372
Number of pages20
JournalInternational Journal of Molecular Sciences
Volume23
Issue number13
DOIs
Publication statusPublished - 1 Jul 2022

Keywords

  • Baicalein
  • intraocular pressure
  • outflow facility
  • trabecular meshwork
  • cell contractility
  • regulatory volume decrease
  • extracellular matrix
  • proteomics
  • glaucoma

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