Conjunctival immunological tolerance in a murine evaporative dry eye model

GALLETTI JEREMÍAS GASTÓN; GUZMÁN MAURICIO; SABBIONE FLORENCIA; GABELLONI MARÍA LAURA; VANZULLI SILVIA; CHIARADÍA PABLO; CASIRAGHI JAVIER; TREVANI ANALÍA SILVINA; GIORDANO MIRTA NILDA

Orlando

Congreso; ARVO 2014 Annual Meeting; 2014

ARVO

Purpose: To assess the state of conjunctival tolerance in a murine model of evaporative dry eye and to evaluate the effect of topical nuclear factor kappa B (NFkB) modulation on disease progression.Methods: A previously reported murine model of evaporative dry eye (Niederkorn JY et al. J Immunol. 2006 Apr 1;176(7):3950-7) was used with 8-week-old Balb/c mice (3 animals per treatment group). Ovalbumin (OVA) was used as a model antigen to assess immunological tolerance. In brief, OVA was instilled daily starting on days 1 and 4 in both eyes of mice under escopolamine- and air draft-induced desiccating stress for 5 days (DS5). In other experiment, topical NFkB inhibitors or vehicle were instilled 3 times a day during DS5. OVA specific T cell responses, as well as tear production and histopathological markers of disease, were evaluated. Conjunctival tolerance to OVA is expressed relative to the systemic T cell response of non-tolerant immunized mice.Results: In the evaporative dry eye model (3 independent experiments), conjunctival tolerance to OVA was observed when antigen was instilled from day 1 (53±3%, p