Lychee seed polyphenol protects blood–retinal barrier by increasing tight joint proteins and inhibiting the activation of TLR4/MYD88/NF-κB-mediated NLRP3 inflammasome

Emerging evidence indicates that blood–retinal barrier (BRB) damage is the main cause of diabetic retinopathy (DR), and the downregulation of tight proteins (TJs) located between endothelial cells and the activation of NLRP3 inflammasome-mediated inflammation in Müller cells result in BRB injury. In this study, we aimed to study the protective effect of lychee seed polyphenol (LSP) on BRB integrity and the mechanism of action. By establishing a cellular model of BRB injury by using high glucose (HG)-induced hRECs or co-culture system of hRECs with MIO-M1 cells, we found that LSP significantly maintained the integrity of monolayer of hRECs as revealed by the decreased PD40 permeability and increased TJs, including ZO-1, Occludin, and Claudin 5. In addition, LSP inhibited the NLRP3 inflammasome activation and the levels of inflammatory cytokines via the TLR4/MYD88/NF-κB pathway. Collectively, this study provides valuable insight into the utilization of LSP in the treatment of DR.