Ganoderma lucidum polysaccharide attenuates retinal ischemia-reperfusion injury by regulating microglial M1/M2 polarization, suppressing neuroinflammation and inhibiting JAK2/STAT3 pathway

Retinal ischemia-reperfusion (RIR) injury is implicated in the pathogenesis of numerous retinal degenerative disorders, resulting in visual impairment or even blindness in millions of individuals worldwide. In recent years, targeting the suppression of microglia-mediated neuroinflammation has emerged as a principal therapeutic strategy for RIR. Ganoderma lucidum polysaccharide (GLP), a pivotal bioactive extract of Ganoderma lucidum, has been demonstrated to possess efficacious anti-neuroinflammatory properties, while the precise impact of it on RIR injury remains incompletely elucidated. In this study, the RIR model was induced in Sprague-Dawley rats by elevating the intraocular pressure to 80 mmHg for 60 min. Our findings revealed that GLP significantly alleviated inflammatory processes by impeding the secretion of pro-inflammatory cytokines while facilitating that of anti-inflammatory cytokines. Moreover, the administration of GLP also promoted the polarization of microglia from the M1 phenotype to the M2 phenotype. Further investigation of the treatment mechanism indicated that the regulatory effects of GLP were presumably mediated by the inhibition of the JAK2/STAT3 signaling pathway. To summarize, we provided a novel insight into the mechanisms by which GLP ameliorated RIR injury, thereby indicating that it could be identified as a promising candidate for the management of RIR-related diseases.