BMSC-Exos affect inflammation and oxidative stress in DR rats by modulating the TLR4/NF-κB signaling pathwayOA

AIM:To investigate the therapeutic effects of bone marrow mesenchymal stem cell-derived exosomes(BMSC-Exos)on diabetic retinopathy(DR)in rats,with a focus on their ability to modulate oxidative stress and inflammatory responses through the TLR4/NF-κB signaling pathway.METHODS:Streptozotocin(STZ)-induced diabetic Sprague-Dawley(SD)rats were randomly divided into four groups:Group 1[normal+phosphate-buffered saline(PBS)],Group 2(normal+Exos),Group 3(DR+PBS),and Group 4(DR+Exos).At the 8 th week after modeling,BMSC-Exos or PBS were injected intravitreally.Retinal tissues were collected at the 16 th week for histological analysis[hematoxylin and eosin(HE)staining],apoptosis detection(TUNEL).Oxidative stress markers[8-OHdG,superoxide dismutase(SOD),and glutathione(GSH)]were assessed,and inflammatory cytokines[enzyme-linked immunosorbent assay(ELISA)for interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α)],and molecular profiling[quantitative polymerase chain reaction(qPCR)for TLR4,NF-κB,and VEGF]were measured.RESULTS:The BMSC-Exos treatment significantly suppressed the activation of the TLR4/NF-κB pathway in DR rats(P<0.01),which was accompanied by reduced retinal vascular leakage(Evans blue assay,P<0.001),decreased apoptosis(TUNEL,P<0.05),and attenuated oxidative stress(elevated SOD and GSH,reduced 8-OHdG,P<0.05).The levels of inflammatory cytokines(IL-6 and TNF-α)were markedly decreased(P<0.01).CONCLUSION:BMSC-Exos alleviate DR by suppressing the TLR4/NF-κB axis,thus reducing oxidative damage,inflammation,and microvascular dysfunction.This research offers a novel therapeutic approach for early-stage DR.