Exposure to particulate matter (PM2.5) weakens corneal defense by downregulating thrombospondin-1 and tight junction proteins

Liangliang Niu; Jiamin Liu; Huan Xu; Binghui Liu; Maomao Song; Chunchun Hu; Rui Jiang; Xinghuai Sun; Yuan Lei

doi:10.1016/j.ecoenv.2024.117276

Exposure to particulate matter (PM_2.5) weakens corneal defense by downregulating thrombospondin-1 and tight junction proteins

Ecotoxicol Environ Saf. 2024 Nov 12:287:117276. doi: 10.1016/j.ecoenv.2024.117276. Online ahead of print.

Authors

Liangliang Niu¹, Jiamin Liu², Huan Xu¹, Binghui Liu², Maomao Song², Chunchun Hu¹, Rui Jiang³, Xinghuai Sun⁴, Yuan Lei⁵

Affiliations

¹ Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; NHC Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200031, China; Ocular Trauma Center, Eye & ENT Hospital, Fudan University, Shanghai 200031, China.
² Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; NHC Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200031, China.
³ Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; NHC Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200031, China; Ocular Trauma Center, Eye & ENT Hospital, Fudan University, Shanghai 200031, China. Electronic address: [email protected].
⁴ Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; NHC Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200031, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China. Electronic address: [email protected].
⁵ Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; NHC Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200031, China. Electronic address: [email protected].

PMID: 39536561
DOI: 10.1016/j.ecoenv.2024.117276

Abstract

Background: Fine particulate matter (PM_2.5) induces ocular surface toxicity through pyroptosis, oxidative stress, autophagy, and inflammatory responses. However, the precise molecular pathways through which PM_2.5 causes corneal damage remain unclear. This study aims to investigate the underlying mechanisms by exposing human corneal epithelial cells (HCECs) to PM_2.5.

Methods: After the morphology and chemical composition analysis of the PM samples, we conducted both in vivo and in vitro experiments to investigate PM_2.5-induced corneal epithelial damage. We assessed corneal barrier function in HCECs using transepithelial electrical resistance (TEER) assays. To explore the molecular mechanisms of PM_2.5-induced corneal epithelial damage, we performed whole-transcriptome resequencing, quantitative RT-PCR, and western blotting in vitro. In addition, we analyzed mouse corneas exposed to concentrated ambient PM_2.5 through immunofluorescence staining to observe the resulting changes in corneal epithelial protein expression in vivo.

Results: Our results showed significant impairment of corneal epithelial barrier function in PM_2.5-treated HCECs, as indicated by decreased TEER values. The expression of thrombospondin-1 (THBS1) and claudin-1, both key factors for maintaining corneal epithelial barrier integrity, was markedly reduced at the gene and protein levels in both in vitro and in vivo PM_2.5 exposure models. Moreover, the levels of tight junction-associated proteins, including occludin, zonula occludens-1 (ZO-1) and ZO-2, essential components of the corneal epithelial barrier, were significantly diminished in PM_2.5-treated HCECs.

Conclusion: PM_2.5 exposure leads to corneal epithelium damage by disrupting tight junction proteins and THBS1 expression. These findings provide insight into potential pathways for PM_2.5-induced ocular toxicity and underscore the need for protective strategies against such environmental pollutants.

Keywords: Corneal epithelial barrier integrity; Fine particulate matter; Thrombospondin-1; Tight junction- associated proteins.