Exosomes derived from platelet-rich plasma mediate hyperglycemia-induced retinal endothelial injury via targeting the TLR4 signaling pathway.

In this study, we aimed to investigate whether exosomes derived from platelet-rich plasma (PRP-Exos) can regulate hyperglycemia-induced retinal injury via targeting the TLR4 signaling pathway. We studied the effects of PRP-Exos on retinal endothelial injury in diabetic rats and human retinal endothelial cells (HRECs) in vitro. Isolated PRP-Exos were observed by transmission electron microscopy and flow cytometry. Samples were obtained from the retinas of rats and cultured HRECs after treatment to analyze reactive oxygen species levels. Immunofluorescence and Western blotting were conducted to assess the levels of adhesion molecules and the TLR4 signaling pathway. The content of CXCL10 in PRP-Exos was analyzed by Western blot. The plasma level of PRP-Exos was greatly increased in diabetic rats. In cultured HRECs, PRP-Exos induced the production of malonyldialdehyde(MDA) and reactive oxygen species(ROS) and inhibited the activity of superoxide dismutase(SOD). Further analysis showed that the activation of the TLR4 pathway by PRP-Exos played a pivotal role in regulating inflammation. The inhibition of the TLR4 pathway by TAK-242 had a robust protective effect on PRP-Exo-induced retinal endothelial injury in vitro and vivo. In addition, PRP-Exo-derived CXCL10 led to retinal endothelial injury, and antagonizing CXCL10 with a CXCL10-neutralizing antibody dramatically attenuated such injury. In summary, PRP-Exos mediate hyperglycemia-induced retinal endothelial injury by upregulating the TLR4 signaling pathway.