Cigarette smoke extract induces ferroptosis in human retinal pigment epithelial cells
Long Zhao,
Ping Wu,
Jing Lu,
Yuxia He,
Qinxin Shu,
Fuying Pan,
Hao Xie,
Xing Wang,
Huan Ju,
Yong Du,
Hui Peng
Affiliations
Long Zhao
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
Ping Wu
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
Jing Lu
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
Yuxia He
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
Qinxin Shu
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
Fuying Pan
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
Hao Xie
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
Xing Wang
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
Huan Ju
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
Yong Du
Corresponding author. The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.; The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
Hui Peng
Corresponding author. The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.; The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
Background: Age-related macular degeneration (AMD) is a common blindness diseases. Retinal pigment epithelium (RPE) dysfunction due to smoking is an essential environmental factor in the pathogenesis of AMD. Ferroptosis is a novel type of iron-dependent programmed cell death (PCD). However, the relationship between cigarette smoke extract (CSE)-induced RPE damage and ferroptosis remains unclear. Methods: In our study, we extracted CSE using a modified device to explore the optimal concentration of CSE, and observed the expression of proteins and molecules after CSE exposure for ARPE-19 cells by protein immunoblotting and assay kits for iron ions and mitochondrial membrane potential (MMP). At the same time, CSE was injected into the vitreous cavity of mice with a microsyringe for AMD modeling to observe the morphology of the retina-RPE-choroid complex and the differences expression of proteins. In addition, the protective effects of ferroptosis inhibitors on CSE-induced RPE cell damage were also investigated by in vivo and in vitro experiments. Results: In this study, we observed that CSE induced cellular damage in a human retinal pigment epithelial cell line (ARPE-19), resulting in ferrous ion (Fe2+) accumulation, an increas in reactive oxygen species (ROS) and lipid peroxidation (LP), a reduction in GSH levels, and the inhibition of Gpx4 expression. In addition, transmission electron microscopy (TEM) of in vivo and in vitro samples showed that after exposure to CSE, the mitochondria of RPE cells were wrinkled, the membrane density was increased, and the number of cristae decreased or cristae were not observed. Conclusions: The results of this study indicate that the ferroptosis inhibitors ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) protect RPE cells from CSE-induced ferroptosis, and this evidence paves the way for AMD studies.
