Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China; Department of Medical Genetics, School of Medicine, Tongji University, Shanghai 200092, China; Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325003, China.
J Hazard Mater. 2023 Oct 5;459:132175. doi: 10.1016/j.jhazmat.2023.132175. Epub 2023 Jul 27.
The increasing use of cosmetics has raised widespread concerns regarding their ingredients. Cysteamine hydrochloride (CSH) is a newly identified allergenic component in cosmetics, and therefore its potential toxicity needs further elucidation. Here, we investigated the in vivo toxicity of CSH during ocular development utilizing a zebrafish model. CSH exposure was linked to smaller eyes, increased vasculature of the fundus and decreased vessel diameter in zebrafish larvae. Moreover, CSH exposure accelerated the process of vascular sprouting and enhanced the proliferation of ocular vascular endothelial cells. Diminished behavior in response to visual stimuli and ocular structural damage in zebrafish larvae after CSH treatment were confirmed by analysis of the photo-visual motor response and pathological examination, respectively. Through transcriptional assays, transgenic fluorescence photography and molecular docking analysis, we determined that CSH inhibited Notch receptor transcription, leading to an aberrant proliferation of ocular vascular endothelial cells mediated by Vegf signaling activation. This process disrupted ocular homeostasis, and induced an inflammatory response with neutrophil accumulation, in addition to the generation of high levels of reactive oxygen species, which in turn promoted the occurrence of apoptotic cells in the eye and ultimately impaired ocular structure and visual function during zebrafish development.
化妆品的使用日益增多，引发了人们对其成分的广泛关注。半胱胺盐酸盐（CSH）是化妆品中一种新发现的变应原成分，因此需要进一步阐明其潜在毒性。在这里，我们利用斑马鱼模型研究了 CSH 在眼部发育过程中的体内毒性。CSH 暴露与斑马鱼幼鱼眼睛变小、眼底血管增多和血管直径减小有关。此外，CSH 暴露加速了血管发芽过程，并增强了眼部血管内皮细胞的增殖。通过光视觉运动反应分析和病理检查分别证实了 CSH 处理后斑马鱼幼鱼对视觉刺激的反应行为下降和眼部结构损伤。通过转录分析、转基因荧光摄影和分子对接分析，我们确定 CSH 抑制了 Notch 受体转录，导致 Vegf 信号激活介导的眼部血管内皮细胞异常增殖。这一过程破坏了眼部的内稳态，并引发了炎症反应，导致中性粒细胞聚集，同时产生大量的活性氧，进而促进了眼部细胞凋亡的发生，最终损害了斑马鱼发育过程中的眼部结构和视觉功能。
