Liping Li1, Chao Xing2, Ji Zhou3, Liangliang Niu1, Bin Luo4,5, Maomao Song1, Jingping Niu4, Ye Ruan6, Xinghuai Sun7,8,9, Yuan Lei10,11. 1. Department of Ophthalmology & Visual Science, Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China. 2. Experimental Research Center, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China. 3. Shanghai Key Laboratory of Meteorology and Health, Shanghai, 200030, China. 4. Institute of Occupational Health and Environmental Health, School of Public Health, Lanzhou University, Lanzhou, 730000, Gansu, China. 5. Shanghai Key Laboratory of Meteorology and Health, Shanghai Meteorological Bureau, Shanghai, China. 6. Institute of Occupational Health and Environmental Health, School of Public Health, Lanzhou University, Lanzhou, 730000, Gansu, China. ruany@lzu.edu.cn. 7. Department of Ophthalmology & Visual Science, Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China. xhsun@shmu.edu.cn. 8. NHC Key Laboratory of Myopia, Chinese Academy of Medical Sciences (Fudan University), and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai, 200031, China. xhsun@shmu.edu.cn. 9. State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China. xhsun@shmu.edu.cn. 10. Department of Ophthalmology & Visual Science, Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China. lilian0167@hotmail.com. 11. NHC Key Laboratory of Myopia, Chinese Academy of Medical Sciences (Fudan University), and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai, 200031, China. lilian0167@hotmail.com.
Abstract
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 PM2.5 on intraocular pressure (IOP). METHODS: To investigate the impact of PM2.5 on IOP and the associated mechanism, C57BL/6 mouse eyes were topically exposed to a PM2.5 suspension for 3 months, and human trabecular meshwork (HTM) cells were subjected to various PM2.5 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 PM2.5-induced damages. RESULTS: The results revealed that the IOP increased gradually after PM2.5 exposure, and upregulations of the NLRP3 inflammasome, caspase-1, IL-1β, and GSDMD protein levels were observed in outflow tissues. PM2.5 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 PM2.5 induced adverse effects. CONCLUSION: 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 and glaucoma. This occurs as a result of increased oxidative stress and the subsequent induction of NLRP3 inflammasome mediated pyroptosis in trabecular meshwork cells.
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 PM2.5 on intraocular pressure (IOP). METHODS: To investigate the impact of PM2.5 on IOP and the associated mechanism, C57BL/6 mouse eyes were topically exposed to a PM2.5 suspension for 3 months, and human trabecular meshwork (HTM) cells were subjected to various PM2.5 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 PM2.5-induced damages. RESULTS: The results revealed that the IOP increased gradually after PM2.5 exposure, and upregulations of the NLRP3 inflammasome, caspase-1, IL-1β, and GSDMD protein levels were observed in outflow tissues. PM2.5 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 PM2.5 induced adverse effects. CONCLUSION: 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 and glaucoma. This occurs as a result of increased oxidative stress and the subsequent induction of NLRP3 inflammasome mediated pyroptosis in trabecular meshwork cells.
Entities:
Keywords:
Human trabecular meshwork cell; Intraocular pressure; NLRP3; PM2.5; Pyroptosis
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