Fructus lycii mitigates oxidative stress in dry age-related macular degeneration models via Nrf2/ARE pathwayOA

AIM:To evaluate the effect of Fructus lycii(FL)aqueous extract on dry age-related macular degeneration(AMD)in mice via the nuclear factor erythroid 2-related factor 2/antioxidant response element(Nrf2/ARE)signaling pathway and investigate the protective effect of FL-containing serum on hydrogen peroxide(H_(2)O_(2))-treated human retinal pigment epithelial cells(ARPE-19)in vitro.METHODS:In vivo dry AMD mouse model was established by intraperitoneal injection of NaIO_(3) solution and treated with aqueous extract of FL.The pathological changes of mouse retinal tissues were observed by electron microscopy;the activity of superoxide dismutase(SOD)and catalase(CAT)in mouse serum was detected by colorimetric method.In vitro dry AMD model was established by H_(2)O_(2) induction of ARPE-19 cells and treated with FL-containing serum.Methylthiazolyldiphenyl-tetrazolium bromide assay and scratch assay were performed to detect cell activity and proliferation ability.Expression of Nrf2,heme oxygenase-1(HO-1),and glutamate-cysteine ligase catalytic subunit(GCLC)in retinal tissues and ARPE-19 cells were detected by Western blot and quantitative real-time polymerase chain reaction(Q-PCR).RESULTS:The in vivo study revealed severe deposits under the retinal pigment epithelium and thickened Bruch’s membrane in dry AMD mice.However,aqueous extract of FL reduced the formation of deposits and decreased the thickness of Bruch’s membrane.SOD and CAT activities were significantly reduced in the serum of dry AMD mice,and aqueous extract of FL upregulated SOD and CAT activities.In addition,gene and protein expression of Nrf2,HO-1,and GCLC were significantly downregulated in dry AMD mice,but significantly upregulated by FL aqueous extract treatment.In vitro studies showed that H_(2)O_(2) inhibited the activity and proliferative capacity of ARPE-19 cells and downregulated the protein and gene expression of Nrf2,HO-1 and GCLC.However,in H_(2)O_(2)-treated ARPE-19 cells,FL-containing serum not only increased cell activity and proliferative capacity,but also upregulated protein and gene expression of Nrf2,HO-1,and GCLC.CONCLUSION:FL reduces oxidative stress in an animal model of dry AMD through the Nrf2/ARE signaling pathway and has a protective effect on dry AMD in vitro and in vivo,providing new insights into the therapeutic use of FL for dry AMD.