Baicalein—A Potent Pro-Homeostatic Regulator of Microglia in Retinal Ischemic Injury

Li Pan, Ying Hon Sze, Menglu Yang, Jing Tang, Siming Zhao, Irvin Yi, Chi-Ho To, Chuen Lam, Dong Feng Chen (Corresponding Author), Kin-Sang Cho (Corresponding Author), Chi-Wai Do (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

Abstract

Retinal ischemia is a common cause of many retinal diseases, leading to irreversible vision impairment and blindness. Excessive neuroinflammation, including microglial activation and T-cell responses, has been identified as a critical factor associated with neurodegeneration in retinal ischemia. Baicalein is a natural flavonoid reported to have broad anti-inflammatory and neuroprotective bioactivities. Herein, the effects of baicalein on microglia activation in vitro and in vivo were investigated. We found that baicalein exhibited robust anti-inflammatory effect on cultured human and mouse microglia, as demonstrated by decreased induction of pro-inflammatory cytokines and the phosphorylation of phosphoinositide 3-kinase (PI3K) and nuclear factor kappa B (NFκB). Proteomic analysis further unraveled baicalein’s effect on modulating IL-17 signaling pathways and its upstream regulator IL-1β. Intravitreal administration of baicalein in the mouse model of retinal ischemia/reperfusion (I/R) injury attenuated microglial activation and retinal T-cell infiltration, particularly the T helper 17 cells. Additionally, baicalein was shown to exert neuroprotective effects by significantly reducing the retinal ganglion cell (RGC) loss after I/R injury, leading to an improved retinal function and spatial vision. These results suggest that baicalein, a natural flavonoid, acts as a negative regulator of activated microglia and immune responses both in vitro and in vivo, effectively alleviating neurodegeneration in retinal I/R injury. This finding indicates that baicalein could be a potential therapeutic agent against currently incurable degenerative retinal diseases.
Original languageEnglish
Article number837497
Pages (from-to)1-16
Number of pages16
JournalFrontiers in Immunology
Volume13
DOIs
Publication statusPublished - 21 Feb 2022

Keywords

  • baicalein
  • neuroinflammation
  • microglia
  • retinal ischemia
  • proteomics
  • Th17 cell
  • IL-1β

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