Kaempferol attenuates retinal ganglion cell death by suppressing NLRP1/NLRP3 inflammasomes and caspase-8 via JNK and NF-κB pathways in acute glaucoma

Abstract

Aims or purpose: Glaucoma is the leading cause of vision loss and blindness in the world. Elucidating the pathogenesis of glaucoma and developing effective treatment should be the priority. Inflammation and oxidative stress play essential roles in glaucoma pathogeneisis. Kaempferol is a natural flavonol and has anti-inflammatory and anti-oxidative activities. In this study, we explored the potential effects of kaempferol on acute glaucoma. Methods: We established the retinal ischemia-reperfusion (I/R) mice model and administrated kaempferol to I/R mice. We monitored the retina thickness change, retinal ganglion cell (RGC) death, caspase-8 and caspase-3 activation, NLRP1/NLRP3 inflammasomes activation, pro-inflammatory cytokines production, and activations of NF-κB and MAPKs signaling pathways. Results: Kaempferol prevented retina thickness change and RGC death in I/R mice. The activations of caspase-8, caspase-3, and NLRP1/NLRP3 inflammasome activation were inhibited by kaempferol. Kaempferol prevented pro-inflammatory cytokines productions in I/R mice. The activation of NF-κB and JNK signaling pathways was also inhibited by Kaempferol in I/R mice. Conclusion: Kaempferol attenuated retinal ganglion cell death by suppressing NLRP1/NLRP3 inflammasomes and caspase-8 via inhibiting NF-κB and JNK pathways in acute glaucoma.