Particulate matter (PM) is a general term for small solid and liquid particles in the atmosphere (a major air pollutant) that vary in size (e.g., PM
2.5–PM
10), composition, and origin.
1,2 There are many different sources of PM, including natural (e.g., forest fires
3) and man made (e.g., diesel engines,
4 industry,
2 wood burning stoves,
5 and agricultural burning
6) types. Exposure to particle pollution is detrimental to health
7 and has economic effects as well.
8 Previous studies have indicated that acute and chronic exposure to PM has increased the morbidity and mortality rate worldwide (e.g., the United States,
9 Europe,
10 and China
11). Specifically, in cities with elevated air pollution levels compared with those without, the individual mortality risk is 26% greater.
1 PM
2.5 is a fine airborne PM with an aerodynamic diameter of <2.5 µm.
12 It is the major outdoor air pollutant in most urban areas worldwide (e.g., China,
13 the United States
14) and a major pollutant in indoor air, especially in households that use biomass fuel for cooking and/or heating.
5,15 These particles are produced mainly from man-made sources and contain molecules composed of sulfates, nitrates, ammonia, carbon, lead, and organic compounds.
11 PM
2.5 is the major and most toxic air pollutant found in environments with heavy traffic and industrial activity and accounts for 5.5% of deaths and $5.1 billion in economic loss annually in urban cities such as Detroit, Michigan.
16 In addition, recent work has confirmed a correlation with modest PM
2.5 increase and mortality in the Medicare population.
17 Owing to its small size, PM
2.5 has an incremental capacity to penetrate different tissues via mucosal membranes (e.g., lung
18). PM
2.5 is strongly associated with the pathogenesis of air pollution-associated diseases including cancer,
19–21 metabolic,
22–24 respiratory,
25–27 and cardiovascular
28,29 diseases, all of which are being investigated. For example, it has been reported that PM
2.5 exposure triggers a variety of maladaptive signaling pathways in the lung,
23,30–32 blood vessels,
33 liver,
22,23,34 and adipose tissues
35 that are associated with oxidative
29,32 and endoplasmic reticulum stress
23,35 and inflammatory responses.
31–33 A mucosal site that has essentially been overlooked is the eye. Specifically, the ocular surface (e.g., cornea
1 and conjunctiva
1) is continually exposed to air pollutants, including PM
2.5, which may lead to an adverse effect on the homeostasis of these tissues. However, little attention has been given to developing models to test the effects of PM
2.5 on ocular disease propensity. Epidemiologic and clinical data suggest that air pollution in which PM
2.5 is a major constituent can cause transient ocular allergies (redness,
1 foreign body sensation,
36 and itching
36). It is also reported that in households that use biomass fuel for cooking and heating, there is a high risk of blindness (e.g., trachoma,
5 cataract
37), especially among young children
5 and females.
37,38 In addition, limited in vitro studies using human corneal epithelial cells (HCET), have suggested, but did not provide mechanisms, by which PM
2.5 may promote autophagy,
39 damage mitochondrial function,
40 decrease cell viability,
41 and cause oxidative damage.
41 If bacteria are present, exposure of mucosal sites to PM may also enhance bacterial stress resistance mechanisms,
42,43 biofilm formation,
42,43 and enhance colonization.
42,43 In this regard, epidemiologic studies strongly suggest that it is biologically plausible to hypothesize that exposure to PM
2.5 is associated with some of the major blinding and painful eye conditions seen worldwide, including the development of corneal ulcers resulting from delayed wound healing after injury or infection.
5 Those studies further suggest that it is difficult to study clinical disease retrospectively and that experimental models are needed to test mechanistically the relationship between PM
2.5 exposure and ocular disease and infection. Other studies reveal a link between PM and increased outpatient visits for several ocular diseases, including allergic conjunctivitis
44 and emergency room visits for keratitis.
45 In this article, we report the effects of PM
2.5 exposure in mouse corneal epithelial cells (MCEC) in vitro, providing evidence that exposure: decreased cell viability and was concentration dependent, increased production of reactive oxygen species (ROS)/reactive nitrogen species (RNS), and inflammatory and oxidative stress associated molecules. A mouse model shows that PM
2.5 exposure together with
Pseudomonas aeruginosa (PA) infection, leads to the upregulation of inflammatory and oxidative stress–associated molecules, a significant increase in infiltrating neutrophils, and an accelerated rate of corneal perforation compared with infected controls. We also show that decreased viability and increased levels of inflammatory molecules after PM
2.5 exposure of three-dimensional (3D) cultured HCET was concentration dependent.