Ferroptosis is involved in the damage of ocular lens under long-term PM 2.5 exposure in rat models and humans.

Autor: Sheng F; Eye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang, China., Gu Y; Eye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang, China., Hao S; Eye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang, China., Liu Y; Eye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang, China., Chen S; Eye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang, China., Lu B; Eye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang, China., Chen L; Eye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang, China., Zhao W; Eye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang, China., Wu D; Eye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang, China., Xu Y; Eye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang, China., Chen R; Eye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang, China., Han Y; Eye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang, China., Lou X; Department of Environmental Health, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, China., Wang X; Department of Environmental Health, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, China., Chen Z; Department of Environmental Health, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, China. Electronic address: zhjchen@cdc.zj.cn., Yao K; Eye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang, China. Electronic address: xlren@zju.edu.cn., Fu Q; Eye Center of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang, China. Electronic address: 2313009@zju.edu.cn.
Jazyk: angličtina
Zdroj: Ecotoxicology and environmental safety [Ecotoxicol Environ Saf] 2024 Dec; Vol. 288, pp. 117397. Date of Electronic Publication: 2024 Nov 28.
DOI: 10.1016/j.ecoenv.2024.117397
Abstrakt: Epidemiological studies show a positive association between air pollution and age-related cataracts, but the pathogenic mechanism remains unclear. This study first demonstrates that fine particulate matter (PM 2.5 ) induces ferroptosis in the lens, leading to morphological and functional disorders, through human, animal, and cellular samples. In 3-week PM 2.5 -exposed rat models (10 µl 1 mg/ml PM 2.5 suspension per eye, 4 times a day), we find that many vacuoles form in the lens equatorial region by analysis of haematoxylin and eosin staining after PM 2.5 exposure. Using iron and glutathione (GSH) assay kits, we found increased Fe 2+ contents and decreased GSH levels in PM 2.5 -exposed rats' lenses. Additionally, the lipid peroxide 4-hydroxynonenal (4-HNE) was also found to be elevated with immunoblot, suggesting ferroptosis is involved. Ferroptosis was also observed in human lens epithelial cells treated with 25, 50, and 100 µg/ml PM 2.5 suspension for 24 h, accompanied by decreased cell viability and migration. Furthermore, we collect about 60 human lens anterior capsule (HLAC) samples for RNA-seq. The results show that compared to HLACs from areas with PM 2.5 concentration ≤30 μg/m³, ferroptosis-related genes expression of those from areas with PM 2.5 concentration ≥35 μg/m³ are significantly altered, such as glutathione peroxidase 4 and STEAP family member 3. Also, human lens in areas with high PM 2.5 concentrations showed elevated levels of transferrin receptor and 4-HNE with immunoblot, and down-regulated expression of connexin 43 (Cx43) through immunofluorescent. These results demonstrate that ferroptosis plays a key role in PM 2.5 -induced cataractogenesis.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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