A Novel Rat Model of Dry Eye Induced by Aerosol Exposure of Particulate Matter

Abstract

Purpose The purpose of this study was to introduce a novel dry eye rat model induced by aerosol exposure of particulate matter (PM). Methods A total of 30 female Sprague Dawley (SD) rats divided into 3 groups: the control group, the low-level exposed group, and the high-level exposed group. The rats in the experience groups were directly exposed to PM samples in the exposure chamber over 14 days. The clinical observation, including tear volume, corneal fluorescein staining, breakup time (BUT), inflammation index, corneal irregularity score, and corneal confocal microscopy. Eyeballs were collected on day 14 for hematoxylin and eosin (H&E) staining and PAS staining. TUNEL assay, CD45, and Ki67 immunostaining was performed and corneal ultrastructural changes were detected by electron microscopy. IL-1β, TNF-α, IFN-γ, and NF-κB Western blot analysis were used to observe the possible pathogenesis. Results In the PM-treated groups, the number of layers in the corneal epithelium and corneal nerve fiber length were significantly decreased compared with that of the control group. The number of corneal epithelial microvilli and chondriosome/desmosomes were drastically reduced in PM-treated groups. Confocal microscopy and CD45 immunohistochemistry showed inflammatory cell infiltration in the PM-treated groups. PM caused apoptosis of corneal and conjunctival epithelial cells while leading to abnormal epithelial cell proliferation, meanwhile, conjunctival goblet cells in the PM-treated group were also significantly reduced. PM significantly increased the levels of IL-1β, TNF-α, IFN-γ, and p-NF-κB-p65 in the cornea. Conclusions Aerosol exposure of PM can reduce the stability of tear film and cause the change of ocular surface, which is similar to the performance of human dry eye, suggesting a novel animal model of dry eye.

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

“…However, when we examined the effects of PM 10 exposure (500 μg/m 3 in a whole body exposure chamber) on tear secretion, no significant change in tear volume was observed after 2 weeks of exposure. Our results also differ from a recent study in female rats exposed to PM in an exposure chamber (500 μg/m 3 for 2 weeks) that showed a significant reduction in tear volume after 14 days [ 48 ]. These differences could be due to the type of particulates used (we used SRM 2787 vs. samples from China), the time of exposure (3 h/d vs. 5 h/d) and different species (mice vs. rats).…”

Toxic External Exposure Leading to Ocular Surface Injury

“…Exposure of mice to fine particulate matter (PM2.5) resulted in dry eye syndrome, as evidenced by increased inflammation in the cornea and conjunctiva, increased tear film damage, the induction of apoptosis in corneal superficial and basal epithelium, and decrease in tear volume [ 60 ]. These results were consistent with results of other studies that found reductions in tear volume, increases in corneal irregularities, and decreases in stability of tear film due to deficits in the mucin-4 layer of the film in mice that were exposed to particulate matter [ 61 , 62 ]. Yang et al placed eye drops with increasing concentration of fine PM into the right eye of C57BL/6 mice and found a dose-dependent decrease in tear secretion and conjunctival goblet cells, consistent with findings in dry eye in humans [ 63 ].…”

Concentration-dependent increase in symptoms due to diesel exhaust in a controlled human exposure study

“…PM and gases routinely interact with exposed surfaces of the body such as the skin [ 39 , 40 ] and eyes [ 41 ] where they may be inflammatory. In the eyes, these pollutants can cause dryness and irritation [ 41 , 42 ] through oxidative stress [ 43 ], mucin disruption, and loss of microvilli, corneal and goblet cells [ 14 , 44 , 45 ]. In the airways, PM 2.5 can enter the alveoli where it induces inflammation and oxidative stress that may result in systemic immune mobilization [ 15 , 46 ].…”