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.

Background: Ambient air pollution is related to the onset and progression of ocular disease. However, the effect of air pollutants on the acute glaucoma remains unclear. Objective: To investigate the effect of air pollutants on the incidence of acute glaucoma (acute angle closure glaucoma and glaucomatocyclitic crisis) among adults. Methods: We conducted a time-stratified case-crossover study based on the data of glaucoma outpatients from January, 2015 to Dec, 2021 in Shanghai, China. A conditional logistic regression model combined with a polynomial distributed lag model was applied for the statistical analysis. Each case serves as its own referent by comparing exposures on the day of the outpatient visit to the exposures on the other 3–4 control days on the same week, month and year. To fully capture the delayed effect of air pollution, we used a maximum lag of 7 days in main model. Results: A total of 14,385 acute glaucoma outpatients were included in this study. We found exposure to PM_2.5, PM₁₀, nitrogen dioxide (NO₂) and carbon monoxide (CO) significantly increased the odds of outpatient visit for acute glaucoma. Wherein the odds of acute glaucoma related to PM_2.5 and NO₂ were higher and more sustained, with OR of 1.07 (95%CI: 1.03–1.11) and 1.12 (95% CI: 1.08–1.17) for an IQR increase over lag 0–3 days, than PM₁₀ and CO over lag 0–1 days (OR:1.03; 95% CI: 1.01–1.05; OR: 1.04; 95% CI: 1.01–1.07). Conclusions: This case-crossover study provided first-hand evidence that air pollutants, especially PM_2.5 and NO₂, significantly increased risk of acute glaucoma.

Purpose: This study aimed to investigate the role and pathophysiological mechanism of ATP binding cassette transporter A1 (ABCA1) in regulating the IOP and aqueous humor outflow. Methods: ABCA1 expression was measured in trabecular meshwork samples obtained from patients with POAG and human donor eyes by Western blot. To further evaluate the functional significance of ABCA1, porcine angular aqueous plexus (AAP) cells, which are equivalent to human Schlemm's canal endothelial cells, were either treated with ABCA1 agonist GW3965 or transduced with lentivirus expressing ABCA1-shRNA. Transendothelial electrical resistance, protein expression, and nitric oxide (NO) concentration were measured. GW3965 was administered by intracameral injection. IOP and aqueous humor outflow facility were also measured. Results: ABCA1 expression was significantly higher in the trabecular meshwork tissue of patients with POAG compared with controls. ABCA1 upregulation in angular aqueous plexus cells decreased the transendothelial electrical resistance in the angular aqueous plexus monolayers accompanied by a 0.56-fold decrease in caveolin-1 expression and a 2.85-fold and 1.17-fold increase in endothelial NO synthase expression and NO concentration, respectively (n = 3, P < 0.05). Conversely, ABCA1 downregulation increased transendothelial electrical resistance and caveolin-1 expression and decreased endothelial NO synthase expression and NO production (n = 3, P < 0.05). GW3965 decreased IOP and significantly increased conventional outflow facility (P < 0.05). Conclusions: Regulation of aqueous humor outflow via the caveolin-1/endothelial NO synthase/NO pathway is a newly defined function of ABCA1 that is different from its traditional role in mediating cholesterol efflux. ABCA1 is a compelling, novel therapeutic candidate for the treatment of glaucoma and ocular hypertension.