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Quercetin Regulates Microglia M1/M2 Polarization and Alleviates Retinal Inflammation via ERK/STAT3 Pathway

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Abstract

Retinal inflammation is a pivotal characteristic observed in various retinal degenerative disorders, notably age-related macular degeneration (AMD), primarily orchestrated by the activation of microglia. Targeting the inhibition of microglial activation has emerged as a therapeutic focal point. Quercetin (Qu), ubiquitously present in dietary sources and tea, has garnered attention for its anti-neuroinflammatory properties. However, the impact of Qu on retinal inflammation and the associated mechanistic pathways remains incompletely elucidated. In this study, retinal inflammation was induced in adult male C57BL/6 J mice through intraperitoneal administration of LPS. The results revealed that Qu pre-treatment induces a phenotypic shift in microglia from M1 phenotype to M2 phenotype. Furthermore, Qu attenuated retinal inflammation and stabilized the integrity of the blood-retina barrier (BRB). In vitro experiments revealed that Qu impedes microglial activation, proliferation, and migration, primarily via modulation the ERK/STAT3 signaling pathway. Notably, these actions of Qu significantly contributed to the preservation of photoreceptors. Consequently, Qu pre-treatment holds promise as an effective strategy for controlling retinal inflammation and preserving visual function.

Graphical Abstract

Exposure to LPS, microglia undergo activation and polarization towards the M1 phenotype. The activation of the cellular ERK/STAT3 signaling pathway resulted in the release of a multitude of cytokines. This cascade disrupts the BRB and damage the photoreceptors. In contrast, Qu intervenes in this process by inhibiting the ERK/STAT3 pathway, facilitating a transition in cellular polarization towards the anti-inflammatory M2 phenotype.

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Funding

This work was supported in part by the National Natural Science Foundation of China (No.81371042), the Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission (No. 22Y11910500), the Shanghai Sailing Program (No. 22YF1406000), the Yunnan Provincial Education Department’s Scientific Research Foundation (No. 2023J0039), the Yunnan Provincial Young and Middle - Aged Academic and Technical Leaders Reserve Talents Project (No. 202305AC160073), and the Yunnan Provincial Department of Science and Technology - Kunming Medical University Joint Fund for Applied Basic Research (No.202301AY070001-086).

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  1. Yue Zou, Junliang Jiang, and Yunqin Li contributed equally to this manuscript

Authors and Affiliations

  1. Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, China NHC Key Laboratory of Myopia (Fudan University) Key Laboratory of Myopia Chinese Academy of Medical Sciences, Fudan University, 83 Fenyang Road, Xuhui District, Shanghai, 200031, China

    Yue Zou, Xinyi Ding & Ling Chen

  2. Yunnan Eye Institute & Key Laboratory of Yunnan Province, Yunnan Eye Disease Clinical Medical Center, Affiliated Hospital of Yunnan University, Yunnan University, Kunming, China

    Yue Zou, Yunqin Li & Fang Fang

  3. Department of Orthopedics & Traumatology, Affiliated Hospital of Yunnan University, Yunnan University, Kunming, China

    Junliang Jiang

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  1. Yue Zou
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Contributions

All authors contributed to the conception and design of the study. YZ: conceptualization, data collection, data analysis, writing—original draft preparation; JJ and YL: conceptualization, data analysis, writing—review and editing, funding acquisition; XD and FF: data collection, data analysis; LC: writing—review and editing, supervision, resources, project administration. All authors reviewed and approved the final version the manuscript.

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Correspondence to Ling Chen.

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Animal studies were performed in compliance with the ARRIVE guidelines. All experimental procedures strictly adhered to the regulations set forth by the Animal Care and Use Committee of Fudan University in Shanghai, China, under approval number 2023DW008.

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Zou, Y., Jiang, J., Li, Y. et al. Quercetin Regulates Microglia M1/M2 Polarization and Alleviates Retinal Inflammation via ERK/STAT3 Pathway. Inflammation (2024). https://doi.org/10.1007/s10753-024-01997-5

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