Abstract
Purpose :
Evaporative dry eye disease (EDED) is a group of disorders characterized by abnormalities in the tear film, most commonly its lipids, that lead to instability and increased evaporation. We recently identified a novel nonpolar lipid (NPL) isolated from the Harderian gland of the rabbit (rNPL593), a species with an exceptionally stable tear film, not identified in the meibum or tears of any other species to date. This preliminary study sought to determine the clinical efficacy of a synthesized version of rNPL593 in a murine model of EDED.
Methods :
A colony of mice deficient in an enzyme that synthesizes long chain wax esters, acyl-CoA: wax alcohol acyltransferase 2 (Awat2), has been established in our laboratory. Loss of Awat2 expression alters the composition and fluidity of the meibum consistent with EDED. The Awat2 KO mice were treated 1-2 times daily in both eyes with the rNPL593 (n=3) or vehicle control (n=2) starting at 2 months of age (initial onset of ocular surface disease). Slit lamp biomicroscopy, disease scoring and tear film diagnostics (phenol red thread test, fluorescein staining) were performed monthly for 1 year. After 1 year, animals were euthanized and eyes were processed for histopathology and von Kossa staining.
Results :
At baseline, all animals exhibited marked meibomian gland dilation with white inspissated meibum, fibrillar material present in the tear film. At subsequent evaluations, progressive white corneal opacities were identified in the interpalpebral fissure of all animals; however, these opacities appeared earlier and were more pronounced and denser in the vehicle-treated animals. Additionally, the dilation of the meibomian glands in the rNPL593-treated animals was reduced over time. Histopathology identified subepithelial basophilic deposits in one vehicle-treated globe, consistent with mineral deposition.
Conclusions :
These results demonstrate that treatment with the rNPL593 decreases clinical signs of EDED, possibly through alteration of the phase transition temperature of the abnormal meibum and/or diffusion into the meibomian gland. Future studies will be focused on determining (1) the mechanisms by which rNPL593 stabilizes the tear film lipid layer and (2) the clinical efficacy in larger cohorts of Awat2 KO mice, as well as canine models of spontaneous DED.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.