A New Non-Human Primate Model of Desiccating Stress-Induced Dry Eye Disease

Dry eye disease (DED), a multifactorial ocular surface disease, is estimated to affect up to 34% of individuals over 50 years old. Although numerous animal models, including rodents and rabbits, have been developed to mimic the pathophysiologic mechanisms involved in the dry eye, there is a lack of non-human primate (NHP) models, critical for translational drug studies. Here, we developed a novel desiccating stress-induced dry eye disease model using rhesus monkeys. The monkeys were housed in a controlled-environment room for 21 to 36 days under humidity, temperature, and airflow regulation. Following desiccating stress, NHPs demonstrated clinical symptoms similar to those of humans, as shown by increased corneal fluorescein staining (CFS) and decreased tear-film breakup. Moreover, corticosteroid treatment significantly reduced CFS scoring, restored TFBUT, and prevented upregulation of tear proinflammatory cytokines as observed in dry eye patients following steroid treatment. These close resemblance of clinical symptoms and treatment responses to those of human DED patients provides great translational value to the NHP model which could serve as a clinically relevant animal model to study the efficacy of the new potential treatment for DED.

Inhibition of Aberrant α(1,2)-Fucosylation at Ocular Surface Ameliorates Dry Eye Disease

Fucosylation is involved in a wide range of biological processes from cellular adhesion to immune regulation. Although the upregulation of fucosylated glycans was reported in diseased corneas, its implication in ocular surface disorders remains largely unknown. In this study, we analyzed the expression of a fucosylated glycan on the ocular surface in two mouse models of dry eye disease (DED), the NOD.B10.H2b mouse model and the environmental desiccating stress model. We furthermore investigated the effects of aberrant fucosylation inhibition on the ocular surface and DED. Results demonstrated that the level of type 2 H antigen, an α(1,2)-fucosylated glycan, was highly increased in the cornea and conjunctiva both in NOD.B10.H2b mice and in BALB/c mice subjected to desiccating stress. Inhibition of α(1,2)-fucosylation by 2-deoxy-D-galactose (2-D-gal) reduced corneal epithelial defects and increased tear production in both DED models. Moreover, 2-D-gal treatment suppressed the levels of inflammatory cytokines in the ocular surface and the percentages of IFN-γ+CD4+ cells in draining lymph nodes, whereas it did not affect the number of conjunctival goblet cells, the MUC5AC level or the meibomian gland area. Together, the findings indicate that aberrant fucosylation underlies the pathogenesis of DED and may be a novel target for DED therapy.