|Title||Mice deficient in toll-like receptor signaling are protected from dry eye ocular surface damage|
|Author, Co-Author||Betty Zhang, Rose Reins, Carolina Lema, Justin Courson, Rachel Redfern|
|Topic||Cornea/anterior segment/external/dry eye|
Purpose: Current understanding of dry eye syndrome (DES) is that a reduced tear volume leads to hyperosmotic tear film and ultimately the production of damaging matrix metalloproteases (MMPs). We hypothesize that toll like receptor (TLRs) activation via MyD88 signaling, is in part, responsible for the production of damaging MMPs on the ocular surface in the mouse model of dry eye.
Methods: Experimental dry eye (EDE) was induced in six to eight week old wild-type (WT), MyD88 knock out (KO), and IL-1R KO C57BL/ mice (n=12/genotype) by scopolamine hydrobromide injections and environmental stress (10-20% humidity and constant air draft). After five days of treatment, tear production and ocular surface damage were accessed using phenol red thread test (PRT) and corneal fluorescein staining respectively. The corneal epithelium was removed and quantitated for MMP protein using a panel of 5 MMPs (2, 3, 8, 9, and 12).
Results: EDE significantly decreased tear production in WT (3.223 ± 0.685mm) and MyD88 KO (1.951 ± 0.778mm) groups (P ≤ 0.001). Corneal fluorescein staining was increased significantly in the WT (pixel intensity increase by 154,337; P ≤ 0.05) and IL-1R KO EDE (pixel intensity increase by 179,114; P ≤ 0.001) groups and not in the MyD88 EDE group (pixel intensity decrease by 52,702.755; P > 0.05). Although not significant, MMP-9 was increased in EDE animals compared to their control in WT (p-value = 0.423), IL-1R KO (p-value = 0.668) and MyD88-KO (p-value = 0.214) mice. Likewise, we observed a similar increase in MMP-8 in EDE animals compared to their control in wild type (p-value = 0.232), IL-1R KO (p-value = 0.042) and MyD88-KO (p-value = 0.078) mice.Conclusion: Mice deficient in TLR signaling (MyD88 KO) were protected from EDE-induced ocular surface damage and also showed the lowest levels of corneal MMP-9 suggesting a potential therapeutic role in blunting dry eye inflammation.
|Affiliation of Co-Authors|