Cysteamine hydrochloride affects ocular development and triggers associated inflammation in zebrafish

Chao Chen; Yuhua Zuo; Hongmei Hu; Yuting Shao; Si Dong; Junquan Zeng; Ling Huang; Ziyi Liu; Qinyuan Shen; Fasheng Liu; Xinjun Liao; Zigang Cao; Zilin Zhong; Huiqiang Lu; Yanlong Bi; Jianjun Chen

doi:10.1016/j.jhazmat.2023.132175

Cysteamine hydrochloride affects ocular development and triggers associated inflammation in zebrafish

J Hazard Mater. 2023 Oct 5:459:132175. doi: 10.1016/j.jhazmat.2023.132175. Epub 2023 Jul 27.

Authors

Chao Chen¹, Yuhua Zuo², Hongmei Hu³, Yuting Shao⁴, Si Dong⁵, Junquan Zeng⁶, Ling Huang⁷, Ziyi Liu⁸, Qinyuan Shen⁸, Fasheng Liu⁸, Xinjun Liao⁸, Zigang Cao⁸, Zilin Zhong⁹, Huiqiang Lu¹⁰, Yanlong Bi¹¹, Jianjun Chen¹²

Affiliations

¹ 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.
² School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325003, China.
³ 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; Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Clinical Research Center of Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an 343009, Jiangxi, China.
⁴ Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
⁵ Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Clinical Research Center of Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an 343009, Jiangxi, China; Department of Internal Medicine and Hematology, Affiliated Hospital of Jinggangshan University, Ji'an 343009, Jiangxi, China.
⁶ Department of Internal Medicine and Hematology, Affiliated Hospital of Jinggangshan University, Ji'an 343009, Jiangxi, China.
⁷ Department of Interventional and Vascular Surgery, Affiliated Hospital of Jinggangshan University, Ji'an 343009, Jiangxi, China.
⁸ Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Clinical Research Center of Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an 343009, Jiangxi, China.
⁹ 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.
¹⁰ Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Clinical Research Center of Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an 343009, Jiangxi, China. Electronic address: Luhuiqlang@jgsu.edu.cn.
¹¹ Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China. Electronic address: biyanlong@tongji.edu.cn.
¹² 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. Electronic address: chenjianjun@tongji.edu.cn.

PMID: 37517235
DOI: 10.1016/j.jhazmat.2023.132175

Abstract

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.

Keywords: Cosmetic product; Cysteamine hydrochloride; Inflammation; Ocular development; Zebrafish.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cysteamine* / toxicity
Endothelial Cells
Inflammation / chemically induced
Molecular Docking Simulation
Zebrafish*

Substances

Cysteamine