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A mouse dry eye model induced by topical administration of the air pollutant particulate matter 10
Juan Li1, Gang Tan2, Xiaoyan Ding3
1Department of Ophthalmology, the Fourth Hospital of Xi'an, Xi'an 710004, Shaanxi Province, China.
Aim:
To introduce a novel dry eye mouse model induced by topical administration of the air pollutant particulate matter 10 (PM10).
Method:
A total of 60 male BALB/c mice were used in this study and divided into two groups: group A (PBS eye drops, n=30) and group B (PM10 eye drop group, n=30). Each treatment was dosed four times a day, every time 50ul with the concentration of 5mg/ml PM10, for 14 consecutive days in the right eye. The clinical manifestations of dry eye were measured before therapy and 4, 7 and 14days post-treatment respectively, which included the tear volume, tear break-up (BUT) time, corneal fluorescein staining, rose bengal staining, Lissamine Green staining and inflammatory index. Eye samples were collected on D14 and examined by histologic light microscopy, transmission electron microscopy (TEM) and scanning electron microscopy (SEM), corneal cytokeration 10 (K10) immunnostaining, and tumor necrosis factor-α (TNF-α), NF-κB-p65 and NF-κB Western Blot analysis.
Results:
At 0d, 7d and 14d, there were no statistical changes in tear volume, BUT after treatment (P>0.05) with PBS in group A. In group B, all items showed statistical differences at each time point (P<0.05). At 14d after therapy, the fluorescein staining score of group B was higher than group A (P<0.05). The score of rose bengal staining and Lissamine Green staining in group B was also higher than that in group A (P<0.05). The number of mean layers of corneal epithelial cells in the group A was significantly lower than that in the group B (P<0.05). TEM and SEM revealed that the number of corneal epithelial microvilli were drastically reduced in group B. The number of corneal chondriosome/desmosomes was also reduced in group B by TEM. PM10 induced apoptosis in the superficial and basal corneal epithelium, and leaded to abnormal differentiation and proliferation of the ocular surface with higher expression levels of K10 and reduced number of goblet cells in the conjunctival fornix in group B. PM10 significantly increased the levels of TNF-α, NF-κB-p65 and NF-κB in the cornea.
Conclusion:
PM10 can damage the tear film function and cause the destruction of the structural organization of ocular surface in mice. Topical administration of PM10 in mice induces ocular surface changes that are similar to those of dry eye in humans, representing a novel model of DES.
Insights
Particulate matter 10 (PM10) eye drops effectively induced dry eye disease (DED) in mice. This novel model mimics human DED symptoms, offering a new tool for research.
Area of Science:
- Ophthalmology
- Environmental Health
- Toxicology
Background:
- Dry eye disease (DED) is a prevalent condition with complex etiologies.
- Existing animal models may not fully replicate human DED pathophysiology.
- Air pollutants, such as particulate matter 10 (PM10), are increasingly implicated in ocular surface disease.
Purpose of the Study:
- To establish and characterize a novel mouse model of dry eye disease (DED).
- To investigate the effects of topical particulate matter 10 (PM10) exposure on the ocular surface.
- To evaluate the utility of this model for studying DED pathogenesis.
Main Methods:
- BALB/c mice were treated with topical PM10 or PBS eye drops for 14 days.
- Ocular surface parameters including tear volume, tear break-up time, and staining were assessed.
- Corneal tissue was analyzed using light microscopy, electron microscopy, and molecular techniques (immunostaining, Western blot).
Main Results:
- PM10 exposure significantly altered tear film function and induced corneal epithelial damage.
- Corneal microvilli, chondriosomes, and desmosomes were reduced in PM10-treated mice.
- PM10 increased ocular surface inflammation, apoptosis, and altered epithelial cell differentiation (K10 expression).
Conclusions:
- Topical PM10 administration effectively induces dry eye-like changes in mice.
- This novel model replicates key features of human DED, including tear film dysfunction and structural damage.
- The PM10-induced mouse model provides a valuable platform for DED research.