Polystyrene nanoplastics induce ocular surface toxicity via endoplasmic reticulum stress

The increasing environmental burden of micro/nanoplastics (M/NPs) has heightened concerns about their potential threat to ocular health, yet the molecular mechanisms underlying M/NPs-induced ocular surface injury remain largely unclear. In this study, we investigated the ocular toxicity of polystyrene nanoplastics (PS-NPs) with a focus on the involvement of endoplasmic reticulum (ER) stress. A mouse ocular exposure model and a human corneal epithelial (HCE-T) cell model were established. Multi-level analyses demonstrated that PS-NPs exposure induced ocular surface toxicity in mice, characterized by diminished tear secretion and corneal epithelial damage. At the cellular level, PS-NPs were internalized by HCE-T cells and accumulated near the ER. Mechanistic investigations revealed that PS-NPs exposure was associated with the activation of the ER stress response, which was accompanied by disrupted redox homeostasis, NF-κB-driven inflammatory activation, promoted apoptosis, and impaired epithelial barrier integrity. Notably, administration of the chemical chaperone 4-phenylbutyric acid (4-PBA), an ER stress inhibitor, substantially attenuated these adverse outcomes in vivo and in vitro. Together, this study establishes a significant association between PS-NPs exposure, ER stress activation, and ocular damage, identifying ER stress as a key and targetable cellular event in the toxicological response to NPs.