Rutin promotes M2 phenotype microglia polarization by suppressing the JAK/STAT3 signaling to protect against retinal ischemia-reperfusion injury

An-Le SU; Shuai ZHAO; Hong-Na ZHU; Ying QIAO; Ting ZHANG

doi:10.2220/biomedres.45.13

Full Paper

Rutin promotes M2 phenotype microglia polarization by suppressing the JAK/STAT3 signaling to protect against retinal ischemia-reperfusion injury

An-Le SU, Shuai ZHAO, Hong-Na ZHU, Ying QIAO, Ting ZHANG

Author information

An-Le SU
Xi’an No.1 Hospital, the First Affiliated Hospital of Northwest University, Shaanxi Provincial Clinical Research Center for Ophthalmology Diseases, Xi’an 710002, Shaanxi, China
Shaanxi institute of Ophthalmology, Shaanxi Key Laboratory of Ophthalmology, Xi’an 710002, Shaanxi, China
Shuai ZHAO
Xi’an No.1 Hospital, the First Affiliated Hospital of Northwest University, Shaanxi Provincial Clinical Research Center for Ophthalmology Diseases, Xi’an 710002, Shaanxi, China
Shaanxi institute of Ophthalmology, Shaanxi Key Laboratory of Ophthalmology, Xi’an 710002, Shaanxi, China
Hong-Na ZHU
Xi’an No.1 Hospital, the First Affiliated Hospital of Northwest University, Shaanxi Provincial Clinical Research Center for Ophthalmology Diseases, Xi’an 710002, Shaanxi, China
Shaanxi institute of Ophthalmology, Shaanxi Key Laboratory of Ophthalmology, Xi’an 710002, Shaanxi, China
Ying QIAO
Xi’an No.1 Hospital, the First Affiliated Hospital of Northwest University, Shaanxi Provincial Clinical Research Center for Ophthalmology Diseases, Xi’an 710002, Shaanxi, China
Shaanxi institute of Ophthalmology, Shaanxi Key Laboratory of Ophthalmology, Xi’an 710002, Shaanxi, China
Ting ZHANG
Xi’an No.1 Hospital, the First Affiliated Hospital of Northwest University, Shaanxi Provincial Clinical Research Center for Ophthalmology Diseases, Xi’an 710002, Shaanxi, China
Shaanxi institute of Ophthalmology, Shaanxi Key Laboratory of Ophthalmology, Xi’an 710002, Shaanxi, China

JOURNAL FREE ACCESS

2024 Volume 45 Issue 1 Pages 13-23

DOI https://doi.org/10.2220/biomedres.45.13

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Abstract

We aimed to investigate the neuroprotective effect of rutin on retinal ganglion cells (RGCs) under ischemia-reperfusion (I/R) conditions and the underlying mechanisms involving microglia polarization and JAK/STAT3 signaling. RGCs isolated from C57/Bl6 mice were co-cultured with BV2 microglial cells under normal or in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) conditions. Rutin’s effects were evaluated by assessing cell viability, apoptosis rates, cytokine levels, microglial polarization markers and JAK/STAT3 phosphorylation levels. The specific target is confirmed through the inhibitory effect of rutin on the respectively activated signaling factors. Furthermore, molecular docking analyses elucidated rutin-JAK1 interactions. OGD/R conditions significantly reduced RGC viability, exacerbated by BV2 co-culture. However, both 1 μM and 5 μM rutin treatment dose-dependently enhanced RGC viability, reduced apoptosis, and suppressed pro-inflammatory cytokine levels. Western blot analysis indicated that rutin promoted the M2 microglial phenotype and suppressed JAK/STAT3 signaling. Notably, rutin selectively inhibited JAK1 phosphorylation without affecting STAT3. Molecular docking highlighted potential interaction sites between rutin and specific JAK1 pseudokinase domain. Rutin exerts neuroprotective effects against retinal I/R injury by promoting M2 microglial polarization, potentially through the selective inhibition of JAK1 phosphorylation within the JAK/STAT3 signaling pathway. These findings provide a foundation for the therapeutic potential of rutin in retinal I/R injuries.

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