Airborne Particulates Affect Corneal Homeostasis and Immunity

Somayajulu, Mallika; Ekanayaka, Sandamali Amarasingha; McClellan, Sharon A.; Bessert, Denise; Pitchaikannu, Ahalya; Zhang, Kezhong; Hazlett, Linda D.

doi:10.1167/iovs.61.4.23

Cited by 21 publications

(10 citation statements)

References 68 publications

(100 reference statements)

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“…S4 ), which is markedly higher than the nation’s air quality standards (35 μg/m 3 ) according to the Environment Protection Agency. However, the PM 2.5 exposure concentrations used in this study are consistent with the common concentration range in the literature [ 50 , 53 , 54 ], which has been calculated based on the particle deposition rate [ 54 ]. For cell culture experiments, cytoxicity was observed with 500 μg/mL PM 2.5 [ 54 ] and 1 mg/mL PM 2.5 , which caused ocular surface damage in rats [ 50 ].…”

Section: Discussionsupporting

confidence: 86%

Airborne particulate matter (PM2.5) triggers ocular hypertension and glaucoma through pyroptosis

Xing

Zhou

et al. 2021

Part Fibre Toxicol

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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.

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Section: Discussionsupporting

confidence: 86%

Airborne particulate matter (PM2.5) triggers ocular hypertension and glaucoma through pyroptosis

Xing

Zhou

et al. 2021

Part Fibre Toxicol

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“…Among the studies on the eye, Cui et al [66] suggested that PM causes a delay in corneal epithelium wound healing and ROS formation might play a critical role in this process. Recently, Somayajulu et al [67] established that PM 2.5 triggers ROS, which results in increased mRNA levels of oxidative stress and inflammation in mouse and human corneal epithelial cells. Although a few studies have suggested that PM triggers ROS generation in corneal and conjunctival epithelium, no studies on ROS and mitochondrial function upon PM have been reported.…”

Section: Discussionmentioning

confidence: 99%

Urban Aerosol Particulate Matter Promotes Necrosis and Autophagy via Reactive Oxygen Species-Mediated Cellular Disorders that Are Accompanied by Cell Cycle Arrest in Retinal Pigment Epithelial Cells

Lee

Kim

Kim³

et al. 2021

Antioxidants

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Urban particulate matter (UPM) is recognized as a grave public health problem worldwide. Although a few studies have linked UPM to ocular surface diseases, few studies have reported on retinal dysfunction. Thus, the aim of the present study was to evaluate the influence of UPM on the retina and identify the main mechanism of UPM toxicity. In this study, we found that UPM significantly induced cytotoxicity with morphological changes in ARPE-19 human retinal pigment epithelial (RPE) cells and increased necrosis and autophagy but not apoptosis. Furthermore, UPM significantly increased G2/M arrest and simultaneously induced alterations in cell cycle regulators. In addition, DNA damage and mitochondrial dysfunction were remarkably enhanced by UPM. However, the pretreatment with the potent reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC) effectively suppressed UPM-mediated cytotoxicity, necrosis, autophagy, and cell cycle arrest. Moreover, NAC markedly restored UPM-induced DNA damage and mitochondrial dysfunction. Meanwhile, UPM increased the expression of mitophagy-regulated proteins, but NAC had no effect on mitophagy. Taken together, although further studies are needed to identify the role of mitophagy in UPM-induced RPE injury, the present study provides the first evidence that ROS-mediated cellular damage through necrosis and autophagy is one of the mechanisms of UPM-induced retinal disorders.

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“…HCET cells (HCE-2 [50.B1], ATCC, Gaithersburg, MA, USA) were cultured in Keratinocyte-serum free medium (Gibco, Grand Island, NY, USA) with 5 ng/mL human recombinant EGF, 0.05 mg/mL bovine pituitary extract, 0.005 mg/mL insulin, and 500 ng/mL hydrocortisone as reported before [ 73 ]. HCEC (primary corneal epithelial cells, ATCC) were cultured in Keratinocyte-serum free medium (Gibco) with 5 ng/mL human recombinant EGF and 0.05 mg/mL bovine pituitary extract as per the manufacturer’s protocol.…”

Section: Methodsmentioning

confidence: 99%

“…An MTT 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (ThermoFisher Scientific, Grand Island, NY, USA) assay was used to test the effects of PM 10 on HCET viability in the presence and absence of SKQ1, per the manufacturer’s protocol and as reported before [ 73 ]. Briefly, 15,000 HCET cells were seeded in a 96-well plate, treated with increasing concentrations of PM 10 (0, 100 and 200 µg/mL) ± 50 nM SKQ1 and incubated for 24 h. At the end of the treatments, 5 mg/mL MTT reagent was added to each well and incubated at 37 °C for 4 h and the media was removed.…”

Section: Methodsmentioning

confidence: 99%

Airborne Exposure of the Cornea to PM10 Induces Oxidative Stress and Disrupts Nrf2 Mediated Anti-Oxidant Defenses

Somayajulu

McClellan

Wright

et al. 2023

IJMS

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The purpose of this study is to test the effects of whole-body animal exposure to airborne particulate matter (PM) with an aerodynamic diameter of <10 μm (PM10) in the mouse cornea and in vitro. C57BL/6 mice were exposed to control or 500 µg/m3 PM10 for 2 weeks. In vivo, reduced glutathione (GSH) and malondialdehyde (MDA) were analyzed. RT-PCR and ELISA evaluated levels of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling and inflammatory markers. SKQ1, a novel mitochondrial antioxidant, was applied topically and GSH, MDA and Nrf2 levels were tested. In vitro, cells were treated with PM10 ± SKQ1 and cell viability, MDA, mitochondrial ROS, ATP and Nrf2 protein were tested. In vivo, PM10 vs. control exposure significantly reduced GSH, corneal thickness and increased MDA levels. PM10-exposed corneas showed significantly higher mRNA levels for downstream targets, pro-inflammatory molecules and reduced Nrf2 protein. In PM10-exposed corneas, SKQ1 restored GSH and Nrf2 levels and lowered MDA. In vitro, PM10 reduced cell viability, Nrf2 protein, and ATP, and increased MDA, and mitochondrial ROS; while SKQ1 reversed these effects. Whole-body PM10 exposure triggers oxidative stress, disrupting the Nrf2 pathway. SKQ1 reverses these deleterious effects in vivo and in vitro, suggesting applicability to humans.

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Airborne Particulates Affect Corneal Homeostasis and Immunity

Cited by 21 publications

References 68 publications

Airborne particulate matter (PM2.5) triggers ocular hypertension and glaucoma through pyroptosis

Airborne particulate matter (PM2.5) triggers ocular hypertension and glaucoma through pyroptosis

Urban Aerosol Particulate Matter Promotes Necrosis and Autophagy via Reactive Oxygen Species-Mediated Cellular Disorders that Are Accompanied by Cell Cycle Arrest in Retinal Pigment Epithelial Cells

Airborne Exposure of the Cornea to PM10 Induces Oxidative Stress and Disrupts Nrf2 Mediated Anti-Oxidant Defenses

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