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Yuan Lei, Liping Li, Ji Zhou, Xinghuai Sun; Airborne particulate matter topical exposure triggers ocular hypertension. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2751.
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© ARVO (1962-2015); The Authors (2016-present)
Over 90% of the global population is exposed to air pollution. Latest epidemiological studies have found that particulate matter (PM), especially PM2.5 (aerodynamic diameter ≤ 2.5 μm), is associated with glaucoma. However, it is controversial as the association is linked to intraocular pressure elevation or retinal damage. This study aims to determine how PM2.5 affects IOP and the underlying molecular mechanism involved.
Atmospheric PM2.5 samples were obtained from May 2016 to Dec 2018 in Lanzhou, China. PM2.5 suspension was given as topical eyedrops (1 mg/mL) to the right mouse eyes (C57BL/6, male, 6 weeks old, n=10) 3 times a day for 104 days, the contralateral left eyes serving as the control. Human trabecular meshwork (HTM) cells (three cell lines) were subjected to various PM2.5 concentrations (25 - 400 mg/mL) for 48 hours. Cell viability, ROS production, NLRP3/caspase-1, IL-1β, and GSDMD expression was measured by western blot or ELISA. HTM cells were pre-treated with N-acetyl-L-cysteine (NAC, 3 mM) for 2 hours before cultured with PM2.5 (100 ug/mL) for 48 hours.
In mouse eyes exposed to PM2.5, IOP elevation was steadily significant from day 30 compared with the controls (n = 10; P < 0.05). Western blot analysis showed that PM2.5 increased the expressions of NLRP3 inflammasome mediated pyroptosis pathway (NLRP3/caspase 1/IL-1β/GSDMD) in the mouse cornea and outflow tissues (NLRP3, n = 3, caspase-1, n = 4, IL-1β, n = 3, GSDMD n = 4, p < 0.05). Cell experiments showed that PM2.5 exposure elevated ROS levels (n = 3, p < 0.05), decreased cell viability (n = 5, p < 0.05) and encouraged cell contraction in HTM cells (n = 3, p < 0.05). Antioxidant NAC improved HTM cell viability (n = 5, p < 0.05), inhibited the activation of the NLRP3 inflammasome axis (n = 3, p < 0.05) and HTM cell contraction (n = 3, p < 0.05).
This study provides novel evidence that PM2.5 has a direct toxic effect on intraocular tissues and may contribute to the initiation and development of ocular hypertension. This occurs as a result of increased oxidative stress and the subsequent induction of the NLRP3 inflammasome mediated pyroptosis signaling pathway in trabecular meshwork cells.
This is a 2021 ARVO Annual Meeting abstract.
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