Abstract: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 8th week after modeling, BMSC-Exos or PBS were injected intravitreally. Retinal tissues were collected at the 16th 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.
