ABSTRACT

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.

摘要

新出现的证据表明，血-视网膜屏障 (BRB) 损伤是糖尿病视网膜病变 (DR) 的主要原因，位于内皮细胞之间的致密蛋白 (TJ) 的下调和 NLRP3 炎症小体介导的 Müller 细胞炎症的激活导致BRB 受伤。本研究旨在研究荔枝籽多酚（LSP）对BRB完整性的保护作用及其作用机制。通过使用高糖 (HG) 诱导的 hRECs 或 hRECs 与 MIO-M1 细胞的共培养系统建立 BRB 损伤的细胞模型，我们发现 LSP 显着保持了 hRECs 单层的完整性，如 PD40 通透性降低所揭示的并增加了 TJ，包括 ZO-1、Occludin 和 Claudin 5。此外，LSP 通过 TLR4/MYD88/NF-κB 通路抑制 NLRP3 炎症小体的激活和炎症细胞因子的水平。总的来说，这项研究为 LSP 在 DR 治疗中的应用提供了宝贵的见解。