Airborne particulate matter (PM 2.5 ) triggers ocular hypertension and glaucoma through pyroptosis

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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 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.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12989-021-00403-4.

Related collections

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Author and article information

Contributors

Ye Ruan: ruany@lzu.edu.cn

Xinghuai Sun: xhsun@shmu.edu.cn

Yuan Lei: lilian0167@hotmail.com , yuan_lei@fudan.edu.cn

Journal

Journal ID (nlm-ta): Part Fibre Toxicol

Journal ID (iso-abbrev): Part Fibre Toxicol

Title: Particle and Fibre Toxicology

Publisher: BioMed Central (London )

ISSN (Electronic): 1743-8977

Publication date (Electronic): 4 March 2021

Publication date PMC-release: 4 March 2021

Publication date Collection: 2021

Volume: 18

Electronic Location Identifier: 10

Affiliations

[1 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Department of Ophthalmology & Visual Science, Eye Institute, Eye & ENT Hospital, Shanghai Medical College, , Fudan University, ; Shanghai, 200031 China

[2 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, 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 ]GRID grid.32566.34, ISNI 0000 0000 8571 0482, Institute of Occupational Health and Environmental Health, School of Public Health, , Lanzhou University, ; Lanzhou, 730000 Gansu China

[5 ]GRID grid.464435.4, ISNI 0000 0004 0593 7433, Shanghai Key Laboratory of Meteorology and Health, , Shanghai Meteorological Bureau, ; Shanghai, China

[6 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, 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

[7 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, , Fudan University, ; Shanghai, 200032 China

Article

Publisher ID: 403

DOI: 10.1186/s12989-021-00403-4

PMC ID: 7934500

PubMed ID: 33663554

SO-VID: 08972603-8b79-41e4-887d-b6b8d697334e

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 9 September 2020

Date accepted : 18 February 2021

Funding

Funded by: Bright Focus Foundation

Award ID: G2018112

Award Recipient : Yuan Lei

Funded by: FundRef http://dx.doi.org/10.13039/501100007279, Shanghai Municipal Health Bureau;

Award ID: XYQ2013083, YL

Award Recipient : Yuan Lei

Funded by: National Natural Science Foundation of China (CN)

Award ID: 81872578

Award Recipient : Ye Ruan

Funded by: National Science Foundation China

Award ID: 81100662, 81371015

Award Recipient : Yuan Lei

Funded by: 211 Project of Fudan University

Award ID: EHF158351

Award Recipient : Yuan Lei

Funded by: Scientific Research Foundation for the Returned Overseas Chinese Scholars (State Education Ministry)

Funded by: FundRef http://dx.doi.org/10.13039/501100012326, International Science and Technology Cooperation Programme;

Award ID: No.2015DFA31340

Award Recipient : Xinghuai Sun

Custom metadata

ScienceOpen disciplines: Toxicology

Keywords: pm2.5,nlrp3,intraocular pressure,human trabecular meshwork cell,pyroptosis

Data availability:

ScienceOpen disciplines: Toxicology

Keywords: pm2.5, nlrp3, intraocular pressure, human trabecular meshwork cell, pyroptosis