Lychee seed polyphenol ameliorates DR via inhibiting inflammasome/apoptosis and angiogenesis in hRECs and db/db mice.

Blood retinal barrier (BRB) damage is an important pathogenesis of diabetic retinopathy, and alleviating BRB damage has become a key target for DR treatment. We previously found that Lycopene seed polyphenols (LSP) maintained BRB integrity by inhibiting NLRP3 inflammasome-mediated inflammation. However, it is still unknown whether LSP inhibits retinal neovascularization with abnormal capillaries and its mechanism of action. Here, we employed db/db mice and hRECs to find that LSP increases the level of glycolipid metabolism, maintains the morphology of retinal endothelial cells and inhibits acellular capillary neogenesis. Mechanistic studies revealed that LSP inhibits the NLRP3 inflammasome, reduces cell apoptosis in retinal tissue, increases tight junction protein (TJ) expression, and reduces vascular endothelial growth factor (VEGF) and Ve-Cadherin in vivo and in vitro. Collectively, this study finds that LSP inhibits inflammation and angiogenesis to improve BRB function to ameliorate DR. [Display omitted] ● Inflammasomes, apoptosis, and angiogenesis coexist in the pathogenesis of DR, and multitargeted intervention is required to achieve good therapeutic effects. ● LSP could exert anti-inflammatory, anti-apoptotic and TJ protective effects in a high glucose environment. ● BRB dysfunction secondary to inflammasomes and apoptosis is a typical pathologic change in DR. ● LSP improved BRB function by inhibiting inflammation, apoptosis and neovascularization to effectively treat DR. [ABSTRACT FROM AUTHOR]