Selenium nanoparticles attenuate retinal pathological angiogenesis by disrupting cell cycle distribution

This study aims to explore the mechanism by which selenium nanoparticles (SeNPs) inhibit retinal neovascularization (RNV) and to identify a more effective treatment for pathological RNV. The characterization and identification of the synthesized selenium nanoparticles (SeNPs) were conducted to investigate their effects on the function of human umbilical vein endothelial cells (HUVECs), retinal blood vessel development in mice, and the impact on oxygen-induced retinopathy. Tritium-labeled thymine was utilized to label newly synthesized DNA both <i>in vivo</i> and <i>in vitro</i>, allowing for the observation of SeNPs’ effects on cell proliferation. Additionally, flow cytometry, immunofluorescence, and western blotting techniques were employed to elucidate the mechanisms by which SeNPs inhibit retinal neovascularization. SeNPs can significantly inhibit the functions of vascular endothelial cells, particularly their proliferation, both <i>in vivo</i> and <i>in vitro</i>. The SeNPs achieve this by modulating the expression of cell cycle-related proteins through the regulation of the PI3K-AKT-p21 axis, which in turn inhibits the transition of the cell cycle from the G1 phase to the S phase. SeNPs may be a novel treatment for the interference of retinal neovascularization.

本研究旨在阐明硒纳米颗粒（SeNPs）抑制视网膜新生血管（RNV）的作用机制，并为病理性视网膜新生血管开发更为有效的治疗方案。本研究对合成的硒纳米颗粒进行表征与鉴定，以探究其对人脐静脉内皮细胞（HUVECs）功能、小鼠视网膜血管发育的影响，以及对氧诱导性视网膜病变的作用。研究采用氚标记胸腺嘧啶对体内（in vivo）及体外（in vitro）新合成的DNA进行标记，以此观测硒纳米颗粒对细胞增殖的影响。此外，本研究还运用流式细胞术、免疫荧光及蛋白质免疫印迹（Western blotting）技术，阐明硒纳米颗粒抑制视网膜新生血管的具体机制。实验结果表明，硒纳米颗粒可在体内及体外显著抑制血管内皮细胞的各项功能，尤其是细胞增殖能力。其作用机制为通过调控PI3K-AKT-p21信号轴，调节细胞周期相关蛋白的表达，进而阻断细胞周期从G1期向S期的转换。综上，硒纳米颗粒有望成为干预视网膜新生血管的新型治疗策略。