Background: Particulate matter (PM) is strongly linked to human health and has detrimental effects on the eye. Studies have, however, focused on the ocular surface, with limited research on the impact of PM_2.5 on intraocular pressure (IOP). Methods: To investigate the impact of PM_2.5 on IOP and the associated mechanism, C57BL/6 mouse eyes were topically exposed to a PM_2.5 suspension for 3 months, and human trabecular meshwork (HTM) cells were subjected to various PM_2.5 concentrations in vitro. Cell viability, NLRP3/caspase-1, IL-1β, and GSDMD expression, reactive oxygen species (ROS) production and cell contractility were measured by western blot, ELISA, cell counting kit-8, ROS assay kit or a cell contractility assay. ROS scavenger N-acetyl-L-cysteine (NAC) and caspase-1 inhibitor VX-765 were used to intervene in PM_2.5-induced damages. Results: The results revealed that the IOP increased gradually after PM_2.5 exposure, and upregulations of the NLRP3 inflammasome, caspase-1, IL-1β, and GSDMD protein levels were observed in outflow tissues. PM_2.5 exposure decreased HTM cell viability and affected contraction. Furthermore, elevated ROS levels were observed as well as an activation of the NLRP3 inflammasome and downstream inflammatory factors caspase-1 and IL-1β. NAC improved HTM cell viability, inhibited the activation of the NLRP3 inflammasome axis, and HTM cell contraction by scavenging ROS. VX-765 showed similar protection against the PM_2.5 induced adverse effects. Conclusion: This study provides novel evidence that PM_2.5 has a direct toxic effect on intraocular tissues and may contribute to the initiation and development of ocular hypertension and glaucoma. This occurs as a result of increased oxidative stress and the subsequent induction of NLRP3 inflammasome mediated pyroptosis in trabecular meshwork cells.

Although studies have demonstrated that fine particulate matter (PM_2.5) induces ocular surface damage, PM2.5 exposure causes cornea toxicity is not entirely clear. The aim of this study is to investigate the role of the nod-like receptor family pyrin domain containing three (NLRP3) inflammasome-mediated pyroptosis in PM_2.5-related corneal toxicity. Human corneal epithelial cells (HCECs) were exposed to different concentrations of PM_2.5, and the cell viability, expressions of NLRP3 inflammasome mediated pyroptosis axis molecules and intracellular reactive oxygen species (ROS) formation were measured in HCECs. Animal experiments were undertaken to topically apply PM_2.5 suspension to mouse eyes for three months and the pyroptosis related molecules in the mouse corneas were measured. RESULTS: Our results showed a dose-dependent decrease of HCEC viability in the PM_2.5-treated cells. NLRP3 inflammasome-mediated pyroptosis axis (NLRP3, ASC, GSDMD, caspase-1, IL-1β, and IL-18) were activated in the PM_2.5-treated HCECs, accompanied by increased ROS formation. Further in vivo study confirmed the activation of this pathway in the mouse corneas exposed to PM_2.5. In conclusion, this study provids novel evidence that PM_2.5 induces corneal toxicity by triggering cell pyroptosis.