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Open accessJournal ArticleDOI: 10.1186/S12989-021-00403-4

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

04 Mar 2021-Particle and Fibre Toxicology (BioMed Central)-Vol. 18, Iss: 1, pp 1-13
Abstract: 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). 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. 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. 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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Topics: Viability assay (56%), Inflammasome (55%), Trabecular meshwork (54%) ... show more

6 results found

Journal ArticleDOI: 10.1063/5.0054075
Matthias Marczynski1, Oliver Lieleg1Institutions (1)
10 Aug 2021-
Abstract: A decade ago, environmental issues, such as air pollution and the contamination of the oceans with microplastic, were prominently communicated in the media. However, these days, political topics, as well as the ongoing COVID-19 pandemic, have clearly taken over. In spite of this shift in focus regarding media representation, researchers have made progress in evaluating the possible health risks associated with particulate contaminations present in water and air. In this review article, we summarize recent efforts that establish a clear link between the increasing occurrence of certain pathological conditions and the exposure of humans (or animals) to airborne or waterborne particulate matter. First, we give an overview of the physiological functions mucus has to fulfill in humans and animals, and we discuss different sources of particulate matter. We then highlight parameters that govern particle toxicity and summarize our current knowledge of how an exposure to particulate matter can be related to dysfunctions of mucosal systems. Last, we outline how biophysical tools and methods can help researchers to obtain a better understanding of how particulate matter may affect human health. As we discuss here, recent research has made it quite clear that the structure and functions of those mucosal systems are sensitive toward particulate contaminations. Yet, our mechanistic understanding of how (and which) nano- and microparticles can compromise human health via interacting with mucosal barriers is far from complete.

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8 Citations

Open accessJournal ArticleDOI: 10.1167/IOVS.62.10.7
Abstract: Purpose To determine the relationship between fine particulate matter (PM2.5) and ocular outcomes such as visual impairment and age-related eye disease. Methods Baseline data were used from the Canadian Longitudinal Study on Aging. The Comprehensive Cohort consisted of 30,097 adults ages 45 to 85 years. Annual mean PM2.5 levels (µg/m3) for each participant's postal code were estimated from satellite data. Ozone, sulfur dioxide, and nitrogen dioxide levels were also estimated. Binocular presenting visual acuity was measured using a visual acuity chart. Intraocular pressure (IOP) was measured in millimeters of mercury using the Reichart Ocular Response Analyzer. Participants were asked about a diagnosis of glaucoma, macular degeneration, or cataract. Logistic and linear regression models were used. Results The overall mean PM2.5 level was 6.5 µg/m3 (SD = 1.8). In the single pollutant models, increased PM2.5 levels (per interquartile range) were associated with visual impairment (odds ratio [OR] = 1.12; 95% confidence interval [CI], 1.02-1.24), glaucoma (OR = 1.14; 95% CI, 1.01-1.29), and visually impairing age-related macular degeneration (OR = 1.52; 95% CI, 1.10-2.09) after adjustment for sociodemographics and disease. PM2.5 had a borderline adjusted association with cataract (OR = 1.06; 95% CI, 0.99-1.14). In the multi-pollutant models, increased PM2.5 was associated with glaucoma and IOP only after adjustment for sociodemographics and disease (OR = 1.24; 95% CI, 1.05-1.46 and β = 0.24; 95% CI, 0.12-0.37). Conclusions Increased PM2.5 is associated with glaucoma and IOP. These associations should be confirmed using longitudinal data and potential mechanisms should be explored. If confirmed, this work may have relevance for revision of World Health Organization thresholds to protect human health.

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Topics: Intraocular pressure (53%), Glaucoma (53%), Visual acuity (52%)

2 Citations

Open accessJournal ArticleDOI: 10.3390/APP11167385
11 Aug 2021-Applied Sciences
Abstract: Mitochondria are the energy factories of cells. Mitochondrial dysfunction directly affects the function and morphology of cells. In recent years, growing evidence has shown that mitochondrial dysfunction plays an important role in neurodegenerative diseases. In the eye, some age-related diseases are considered to be neurodegenerative diseases, such as primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD). Here, we review the mechanisms of mitochondrial damage, post-injury repair, and the roles of mitochondria in various tissues of the eye. In the following sections, the potential for treating glaucoma by reducing mitochondrial damage and promoting post-injury repair is also discussed.

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Topics: Neurodegeneration (52%)

1 Citations

Open accessJournal ArticleDOI: 10.1016/J.ECOENV.2021.112963
Liping Li1, Ji Zhou1, Wenpei Fan2, Liangliang Niu1  +4 moreInstitutions (2)
Abstract: Epidemiological studies suggest that ambient particulate matter exposure may be a new risk factor of glaucoma, but it lacks solid experimental evidence to establish a causal relationship. In this study, young mice (4 weeks old) were exposed concentrated ambient PM2.5 (CAP) for 9 months, which is throughout most of the life span of a mouse under heavy pollution. CAP was introduced using a versatile aerosol concentration enrichment system which mimics natural PM2.5 exposure. CAP exposure caused a gradual elevation of intraocular pressure (IOP) and an increase in aqueous humor outflow resistance. In the conventional outflow tissues that regulates IOP, inducible nitric oxide synthase (iNOS) was up-regulated and 3-nitrotyrosine (3-NT) formation increased. At the cellular level, PM2.5 exposure increased the transendothelial electrical resistance of cells that control IOP (AAP cells). This is accompanied by increased reactive oxygen species (ROS), iNOS and 3-NT levels. Peroxynitrite scavenger MnTMPyP successfully treated the IOP elevation and restored it to normal levels by reducing 3-NT formation in outflow tissues. This study provides the novel evidence that in young mice, lifetime whole-body PM2.5 exposure has a direct toxic effect on intraocular tissues, which imposes a significant risk of IOP elevation and may initiate the development of ocular hypertension and glaucoma. This occurs as a result of protein nitration of conventional aqueous humor outflow tissues.

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Topics: Intraocular pressure (52%)

Open accessJournal ArticleDOI: 10.3390/BIOM11081239
19 Aug 2021-
Abstract: Glaucoma is a group of optic neuropathies characterised by the degeneration of retinal ganglion cells, resulting in damage to the optic nerve head (ONH) and loss of vision in one or both eyes. Increased intraocular pressure (IOP) is one of the major aetiological risk factors in glaucoma, and is currently the only modifiable risk factor. However, 30-40% of glaucoma patients do not present with elevated IOP and still proceed to lose vision. The pathophysiology of glaucoma is therefore not completely understood, and there is a need for the development of IOP-independent neuroprotective therapies to preserve vision. Neuroinflammation has been shown to play a key role in glaucoma and, specifically, the NLRP3 inflammasome, a key driver of inflammation, has recently been implicated. The NLRP3 inflammasome is expressed in the eye and its activation is reported in pre-clinical studies of glaucoma. Activation of the NLRP3 inflammasome results in IL-1β processing. This pro inflammatory cytokine is elevated in the blood of glaucoma patients and is believed to drive neurotoxic inflammation, resulting in axon degeneration and the death of retinal ganglion cells (RGCs). This review discusses glaucoma as an inflammatory disease and evaluates targeting the NLRP3 inflammasome as a therapeutic strategy. A hypothetical mechanism for the action of the NLRP3 inflammasome in glaucoma is presented.

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Topics: Glaucoma (62%), Retinal ganglion (57%), Inflammasome (56%) ... show more


54 results found

Open accessJournal ArticleDOI: 10.1016/J.TIBS.2016.09.002
Yuan He1, Hideki Hara1, Gabriel Núñez1Institutions (1)
Abstract: Members of the nucleotide-binding domain and leucine-rich repeat (LRR)-containing (NLR) family and the pyrin and HIN domain (PYHIN) family can form multiprotein complexes termed 'inflammasomes'. The biochemical function of inflammasomes is to activate caspase-1, which leads to the maturation of interleukin 1 beta (IL-1β) and IL-18 and the induction of pyroptosis, a form of cell death. Unlike other inflammasomes, the NLRP3 inflammasome can be activated by diverse stimuli. The importance of the NLRP3 inflammasome in immunity and human diseases has been well documented, but the mechanism and regulation of its activation remain unclear. In this review we summarize current understanding of the mechanism and regulation of NLRP3 inflammasome activation as well as recent advances in the noncanonical and alternative inflammasome pathways.

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Topics: Inflammasome (65%), AIM2 (63%), Caspase 1 (58%) ... show more

1,108 Citations

Open accessJournal ArticleDOI: 10.1111/J.1600-065X.2011.01044.X
Abstract: Programmed cell death is a necessary part of development and tissue homeostasis enabling the removal of unwanted cells. In the setting of infectious disease, cells that have been commandeered by microbial pathogens become detrimental to the host. When macrophages and dendritic cells are compromised in this way, they can be lysed by pyroptosis, a cell death mechanism that is distinct from apoptosis and oncosis/necrosis. Pyroptosis is triggered by Caspase-1 after its activation by various inflammasomes and results in lysis of the affected cell. Both pyroptosis and apoptosis are programmed cell death mechanisms but are dependent on different caspases, unlike oncosis. Similar to oncosis and unlike apoptosis, pyroptosis results in cellular lysis and release of the cytosolic contents to the extracellular space. This event is predicted to be inherently inflammatory and coincides with interleukin-1β (IL-1β) and IL-18 secretion. We discuss the role of distinct inflammasomes, including NLRC4, NLRP3, and AIM2, as well as the role of the ASC focus in Caspase-1 signaling. We further review the importance of pyroptosis in vivo as a potent mechanism to clear intracellular pathogens.

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Topics: Pyroptosis (71%), Caspase 1 (63%), Caspase (54%) ... show more

711 Citations

Journal ArticleDOI: 10.1146/ANNUREV-CELLBIO-101011-155745
Mohamed Lamkanfi1, Vishva M. Dixit2Institutions (2)
Abstract: Inflammasomes are a set of intracellular protein complexes that enable autocatalytic activation of inflammatory caspases, which drive host and immune responses by releasing cytokines and alarmins into circulation and by inducing pyroptosis, a proinflammatory cell death mode. The inflammasome type mediating these responses varies with the microbial pathogen or stress factor that poses a threat to the organism. Since the discovery that polymorphisms in inflammasome genes are linked to common autoimmune diseases and less frequent periodic fever syndromes, inflammasome signaling has been dissected at the molecular level. In this review, we present recently gained insight on the distinct inflammasome types, their activation and effector mechanisms, and their modulation by microbial virulence factors. In addition, we discuss recently gained knowledge on the role of deregulated inflammasome activity in human autoinflammatory, autoimmune, and infectious diseases.

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Topics: AIM2 (65%), Inflammasome (65%), NALP3 (61%) ... show more

667 Citations

Journal ArticleDOI: 10.1016/S0161-6420(95)31054-8
I. Dielemans1, Johannes R. Vingerling1, D. Algra1, Albert Hofman1  +2 moreInstitutions (1)
01 Jan 1995-Ophthalmology
Abstract: Purpose: The purpose of this study is to investigate the association of primary open-angle glaucoma (POAG), intraocular pressure (IOP), and systemic blood pressure. Methods: Subjects participating in the Rotterdam Study (n = 4187, 55 years of age and older) were examined according to standard protocols, including a medical history interview, IOP measurement, perimetry, funduscopy, and blood pressure measurement. Primary open-angle glaucoma was defined by the presence of a glaucomatous visual field defect. Additionally, the distinction was made between high-tension glaucoma, defined as POAG with an IOP of more than 21 mmHg, and normal-tension glaucoma, defined as POAG with an IOP of 21 mmHg or less. The relation between blood pressure and hypertension with IOP, POAG, high-tension glaucoma, and normal-tension glaucoma was studied by means of regression analysis. Results: A systolic blood pressure or diastolic blood pressure that was 10 mmHg higher was associated with an IOP that was, on average, 0.23 mmHg (95% confidence interval [CI], 0.19–0.27) or 0.24 mmHg (95% CI, 0.16–0.32) higher, respectively. The presence of hypertension was associated with a higher mean IOP of 0.66 mmHg (95% CI, 0.39–0.93). A higher systolic blood pressure of 10 mmHg was associated with an odds ratio of 1.22 (95% CI, 1.03-1.46) for high-tension glaucoma and 0.90 (95% CI, 0.72–1.12) for normal-tension glaucoma. Hypertension was associated with an odds ratio of 2.33 (95% CI, 0.99–5.47) for high-tension glaucoma and 0.77 (95% CI, 0.22–2.72) for normal-tension glaucoma. Conclusion: Systemic blood pressure and hypertension are associated with IOP and high-tension glaucoma. No association was found between blood pressure or hypertension and normal-tension glaucoma.

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Topics: Intraocular pressure (63%), Open angle glaucoma (62%), Glaucoma (62%) ... show more

332 Citations

Open accessJournal ArticleDOI: 10.1161/HYPERTENSIONAHA.117.07802
Tomasz J. Guzik1, Rhian M. Touyz1Institutions (1)
07 Aug 2017-Hypertension
Abstract: Age-related decline in function is a physiological phenomenon occurring in all organ systems. However, acceleration and early occurrence of this process are observed in cardiovascular pathologies, including hypertension.1,2 In the vascular system, this is characterized by progressive pathological remodeling with stiffening,3 typically associated with extracellular matrix (ECM) alterations in collagen and elastin.4 This is, in part, dependent on cellular senescence and growth arrest.5 Although hypertension and atherosclerosis are associated with accumulation of cellular senescence markers in the vascular wall, these conditions are often associated with vascular dysfunction rather than simple loss of proliferative capacity.6 For example, risk factors for cardiovascular disease, such as hypertension, smoking, hyperlipidaemia, or diabetes mellitus are associated with accelerated decline of vascular function.2 This is why vascular age determination has been introduced in key clinical guidelines for cardiovascular prevention, to indicate to the patient how their lifestyle contributes to the acceleration of vascular function deterioration.7 Oxidative stress and inflammation, key mechanisms of endothelial dysfunction and arterial damage, link these risk factors to vascular disease, arterial stiffness, and aging. These underlie macro- and microangiopathy, renal dysfunction, cardiac ischemia, and cognitive decline (Figure). Several novel pathways regulating these mechanisms of accelerated vascular aging have been elucidated in recent issues of Hypertension and are further discussed in the present Best Papers in Hypertension review. Figure. Central role of oxidative stress in accelerated vascular aging in hypertension. AT1R indicates angiotensin II receptor type 1; BH2, dihydrobiopterin; BH4, tetrahydrobiopterin; BMP, bone morphogenic protein; CypD, cyclophilin D; eNOS, endothelial NO synthase; ET1R, endothelin 1 receptor; H2O2, hydrogen peroxide; MMP, matrix metalloproteinase; Nox, NADPH oxidase; O2−., superoxide anion; RANTES, regulated on activation, normal T cell expressed and secreted chemokine; and SmgGDS, GTP-binding protein dissociation …

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237 Citations