Grape Seed Extract Inhibits NLRP3 Inflammasome Activation In Retinal Pigment Epithelial Cells

With the increase of age,?-amyloid(A?)gradually accumulates in retinal tissues,leading to oxidative stress in cells,activating inflammasome,and promoting the overexpression of inflammatory cytokines,which are important factors that induce visual impairment in the elderly.Retinal pigment epithelium(RPE)is a layer of pigment cells that closely adheres to the sensory nerves of the retina and plays an important role in maintaining the normal function of visual cells.RPE cells are susceptible to oxidative damage.Supplementing antioxidants through diet is an important means to inhibit oxidative damage to RPE cells and protect retinal function.Grape seed extract(GSE)is rich in polyphenol antioxidants and has a high-efficiency free-scavenging activity.It is an important dietary supplement to prevent age-related retinopathy,but its mechanism of action is not completely clear.In this paper,by constructing A?_(1-40)-induced retinal tissue inflammation model and RPE cell inflammation model in mice,the effects of GSE on A?_(1-40)-induced activation of NLRP3 inflammasome in RPE cells and their mechanisms were further explored.The main research contents and results include:GSE has inhibitory effect on A?_(1-40)-induced over-expression of pro-inflammatory cytokines and activation of NLRP3 inflammasome in mouse retinal tissue.After intragastric administration of GSE mice,the concentrations of IL-18 and IL-1?in the vitreous decreased by 20%and15%compared with the model group,and the expression levels of NLRP3,IL-1?and Caspase-1 in RPE-choroidal tissue were lower than those in the model group.They decreased by 60%,41.6%and 60%respectively.GSE has an inhibitory effect on A?_(1-40)-induced activation of NLRP3inflammasome in ARPE-19 cells.GSE down-regulated the expression of NLRP3,Caspase-1,and IL-1?in APE-19 cells induced by A?_(1-40),and showed a dose effect.GSE inhibits the expression of A?_(1-40)-induced endoplasmic reticulum stress-related molecules through the unfolded protein response partner molecule Bip.In ARPE-19 cells that silenced Bip expression,GSE had no significant inhibitory effect on A?_(1-40)-induced ATF6 and p-IRE1 protein expression.GSE inhibits the expression of NLRP3 inflammasome and pro-inflammatory cytokines in ARPE-19 cells induced by A?_(1-40)through Bip.GSE can reduce the expression of NLRP3,Caspase-1,and IL-1?in A?_(1-40)-induced ARPE-19 cells.However,in ARPE-19 cells that silence Bip expression,GSE promotes the NLRP3 inflammasome.Expression,and up-regulated inflammatory cytokines IL-6 and IL-8 m RNA levels.To sum up,GSE can inhibit the expression of inflammatory cytokines by inhibiting the activation of NLRP3 inflammasome,and finally achieve the effects of inhibiting cellular inflammasome responses and alleviating retinal damage.