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

• Published in: Experimental eye research Vol. 189; p. 107813
• Main Authors: Zhang, Wei, Dong, Xue, Wang, Tian, Kong, Yichun
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2019
• Subjects: Animals; Apoptosis; Blotting, Western; Cells, Cultured; Diabetes Mellitus, Experimental; Diabetic Retinopathy - genetics; Diabetic Retinopathy - metabolism; Diabetic Retinopathy - pathology; Endothelium, Vascular - metabolism; Endothelium, Vascular - ultrastructure; Exosomes; Exosomes - metabolism; Gene Expression Regulation; Humans; Hyperglycemia - metabolism; Hyperglycemia - pathology; Immunohistochemistry; Microscopy, Electron, Transmission; Platelet-Rich Plasma - metabolism; Platelets; Rats; Reactive oxygen species; Reactive Oxygen Species - metabolism; Retinal endothelial injury; Retinal Vessels - metabolism; Retinal Vessels - ultrastructure; Signal Transduction; TLR4; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Reactive oxygen species; Retinal endothelial injury; Exosomes; Platelets; TLR4
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2019.107813

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. •We firstly studied the effects of PRP-Exos on retinal endothelial injury in diabetic rats and HRECs in vitro.•The activation of the TLR4 pathway by PRP-Exos played a pivotal role in regulating inflammation.•PRP-Exos-derived CXCL10 led to retinal endothelial injury and antagonizing CXCL10 dramatically attenuated such injury.•PRP-Exos mediate hyperglycemia-induced retinal endothelial injury by upregulating the TLR4 signaling pathway.