Abstract
Purpose :
MGD is a leading cause of evaporative dry eye disease and is more severe in ocular surface immune diseases (OSID), such as chronic ocular allergy. Prolonged obstruction of MG orifices is common in OSIDs and can persist despite treatment with anti-inflammatory drugs. Hence, a better understanding of MGD chronicity in the OSID setting is needed to help address this disease burden. To this end, we interrogated the potential chronicity of MGD with our established mouse model of chronic like allergic eye disease (AED) in which MG obstruction is a cardinal feature (Reyes NJ et al., 2018).
Methods :
AED was induced in C57BL/6 mice at 9 wk of age by immunizing with ovalbumin (OVA) in aluminum hydroxide (Alum) and pertussis toxin. After 14 days rest, mice were challenged topically with OVA, once daily for 7 days. At the end of this “challenge phase," and weekly thereafter for 14 weeks, AED and age-matched naïve mice were clinically evaluated for allergy scores (i.e., redness, chemosis, tearing, lid edema). Clinical MG orifice obstruction (plugging) was also scored (1+ = flat; 2+ = enlarged; 3+ = enlarged and raised orifices), as previously described (Singh PP et. al., 2021). Following euthanasia, conjunctivae were collected for flow cytometry and meibography was performed on resected eye lids.
Results :
As expected, AED mice had peak allergy scores at the end of the challenge phase and significantly more 3+ MG plugs relative to naïve age matched mice. Allergy scores then gradually resolved to naïve levels by 5 weeks post challenge phase. Congruently, the conjunctival leukocyte infiltration subsided to naïve levels at 14 weeks post challenge phase. However, MG obstruction persisted out to 14 weeks, although plug scores were below peak levels. Also, meibography showed remarkable MG atrophy, including gland drop-out, as compared to age matched naïve mice at 14 weeks.
Conclusions :
Our results indicate that MGD persists to at least 14 weeks past the challenge phase in the AED model. As inflammation had subsided by this timepoint, our findings suggest that the inflammatory event caused by the challenge phase leads to chronic MGD.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.