Ecotoxicology and Environmental Safety (Nov 2024)
Exposure to particulate matter (PM2.5) weakens corneal defense by downregulating thrombospondin-1 and tight junction proteins
Abstract
Background: Fine particulate matter (PM2.5) induces ocular surface toxicity through pyroptosis, oxidative stress, autophagy, and inflammatory responses. However, the precise molecular pathways through which PM2.5 causes corneal damage remain unclear. This study aims to investigate the underlying mechanisms by exposing human corneal epithelial cells (HCECs) to PM2.5. Methods: After the morphology and chemical composition analysis of the PM samples, we conducted both in vivo and in vitro experiments to investigate PM2.5-induced corneal epithelial damage. We assessed corneal barrier function in HCECs using transepithelial electrical resistance (TEER) assays. To explore the molecular mechanisms of PM2.5-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 PM2.5 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 PM2.5-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 PM2.5 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 PM2.5-treated HCECs. Conclusion: PM2.5 exposure leads to corneal epithelium damage by disrupting tight junction proteins and THBS1 expression. These findings provide insight into potential pathways for PM2.5-induced ocular toxicity and underscore the need for protective strategies against such environmental pollutants.