Abstract
Purpose :
Dry eye disease (DED) is characterized by tear film imbalance, causing ocular symptoms such as instability, hyperosmolarity, inflammation, and neurosensory abnormalities. Inflammation, particularly through the inflammasome pathway and pyroptosis activation, plays a crucial role in ocular surface damage in DED. Our research group presented caspase-1 as a potential biomarker for detecting ocular surface damage in DED patients and those using anti-glaucoma medications. The commonly used preservative benzalkonium chloride (BAC) in ophthalmic preparations exacerbates ocular surface issues by disrupting the tear film's lipid layer, leading to corneal epithelial cell loss, inflammatory cytokine infiltration, and tear film disruption ultimately resulting in DED. This study aims to investigate the inflammasome response in a benzalkonium chloride-induced dry eye disease mouse model.
Methods :
C57/BL6 mice (n=3/group) underwent daily treatment with 10µl of 0.2% Benzalkonium Chloride (treatment group) and 10µl ultra purified water (control group) for a duration of 14 days. Fluorescein staining and slit lamp examinations were conducted prior to treatment, and at intervals of 7 and 14 days. Corneal inflammation activation was evaluated through western blot analysis and quantitative polymerase chain reaction (qPCR).
Results :
In mice treated with BAC, western blot assays revealed a trend of increase in the adaptor protein ASC compared to mice treated solely with the vehicle. Additionally, both qPCR and western blot analyses demonstrated a significant elevation of caspase-1 (cas-1) (p=0.0448) in BAC-treated mice compared to the control group. The qPCR assay further indicated a significant upregulation of caspase-1 (p=0.0266) and IL-1β (p=0.0304) in mice subjected to BAC treatment.
Conclusions :
The current study demostrates the use of C57/BL6 mice treated with BAC as a model for investigating the role of the inflammasome in DED. Elevated inflammasome protein levels and RNA markers show the model's potential to comprehend and address pyroptotic-related DED pathology. These findings provide valuable insights into our understanding of the complex interplay between inflammation and the inflammasome in DED.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.