Tear hyperosmolarity acts as a disruptor of ocular surface immune tolerance in the context of dry eye disease

GALLETTI JEREMÍAS GASTÓN; MIGLIO, MAXIMILIANO S.; GUZMÁN MAURICIO; KEITELMAN IRENE; SABBIONE FLORENCIA; GIORDANO MIRTA NILDA; TREVANI ANALÍA SILVINA

Congreso; ARVO 2020 ANNUAL MEETING; 2020

Purpose : Tear hyperosmolarity is commonly detected in dry eye disease (DED), but its exact role in disease progression is incompletely understood. On the other hand, breakdown of ocular surface tolerance (homeostasis) has been reported in DED models but the trigger remains unknown. The purpose of this work was to evaluate whether hyperosmolar stress could affect ocular surface homeostasis in mice.Methods : 8-to-12 week-old Balb/c mice were instilled isoosmolar (0.3 Osm) or hyperosmolar (3 Osm) saline on both eyes 3 times daily for 5 days to induce hyperosmolar stress (HS). Ovalbumin (OVA) was also instilled as a surrogate antigen or OVA-pulsed dendritic cells (DCs) were subconjunctivally injected at different time points. Induced T cell responses were measured after subcutaneous immunization with OVA by the delayed-type hypersensitivity (DTH) assay. In addition, T cells in draining lymph nodes (day 5) were evaluated by flow cytometry.Results : Compared to non-instilled immunized mice, OVA-instilled mice developed reduced DTH responses (i.e. were tolerized), as did their OVA+saline instilled cage mates (p