MODULATION OF NFKB ACTIVATION AS A THERAPEUTIC TARGET IN EYE DROP PRESERVATIVE TOXICITY

GALLETTI J; GUZMAN M; SABBIONE F; GABELLONI ML,; CHIARADIA P; CASIRAGHI J; TREVANI AS; GIORDANO M

Los Cocos, Córdoba

Congreso; LXI Reunión Anual de la Sociedad Argentina de Inmunología; 2013

Sociedad Argentina de Inmunología

Introduction: Ocular instillation of eye drop preservatives affects conjunctival tolerance in a murine model, but the underlying mechanisms and therapeutic potential remain unexplored. Objective: To evaluate if topical NFkB modulation can mitigate the disruptive immune effect of benzalkonium chloride (BAK) on the ocular surface. Study design: Balb/c mice were given ovalbumin (OVA) alone or with 0.01% BAK (B+O) daily for 5 days in both eyes, with and w/o nuclear factor κB (NFκB) pathway inhibitors: pyrrolidine dithiocarbamate (PDTC) and sulfasalazine (SSZ). On day 7, mice were immunized intraperitoneally with OVA in alum to evaluate the systemic response on day 14 as OVA-induced splenocyte proliferation by thymidine incorporation. To model in vitro the ocular surface epithelium, Pam212 cells were exposed for 15 min to different BAK concentrations (0.00001%-0.01%), then cultured for 96 h with syngeneic T cells and finally the expression of major histocompatibility complex class II (MHC-II) as activation marker was assayed. Results: OVA instillation induced conjunctival tolerance (43±9% of control systemic response, p