| First Author | Hisey EA | Year | 2024 |
| Journal | Ocul Surf | Volume | 34 |
| Pages | 489-503 | PubMed ID | 39414024 |
| Mgi Jnum | J:359571 | Mgi Id | MGI:7787176 |
| Doi | 10.1016/j.jtos.2024.10.003 | Citation | Hisey EA, et al. (2024) Meibomian gland lipid alterations and ocular surface sequela in Awat2 knockout murine model of meibomian gland dysfunction and evaporative dry eye disease. Ocul Surf 34:489-503 |
| abstractText | PURPOSE: There is an urgent need for animal models of meibomian gland dysfunction (MGD) and evaporative dry eye disease (EDED) to understand their pathophysiology and investigate novel therapeutics. This study sought to further define the acyl-CoA: wax alcohol acyltransferase 2 knockout (Awat2 KO) mouse as a model of EDED using a combination of novel clinical, biochemical, and biophysical endpoints. METHODS: Wildtype and Awat2 KO mice between 1 and 18 months of age were used. Ocular examinations and advanced imaging were performed. The lipidomic composition and in situ melting temperature of meibum were determined. qPCR was performed to define ocular surface gene and pro-inflammatory transcript expression. Dynamic contact angle goniometry was performed to assess the adherence capability of the ocular surface. RESULTS: Awat2 KO mice have mild, white, hyperreflective corneal opacities of the anterior stroma and significantly enlarged apical epithelial cells (P = 0.0004). In Awat2 KO meibum, wax esters were 9-10 times lower than in wildtype meibum. Additionally, meibum melting temperature increased from 32 degrees to 47 degrees C (P < 0.0001), leading to impaired meibum secretion and dilation of the central duct. Awat2 KO corneal epithelia had significantly decreased mucin expression (Muc1 and Muc4, P = 0.0043) and increased interferon-gamma production (P = 0.0303). Awat2 KO globes have a significantly shortened time of droplet adherence to their ocular surface (P = 0.0053), indicating a decreased tear film adherence capacity. Wildtype corneal epithelia does not express Awat2, indicating that the EDED phenotype is secondary to the loss of Awat2 from the meibomian glands. CONCLUSIONS: Awat2 KO mice recapitulate many of features of human MGD and EDED, representing a model to test novel therapeutics. |
