COMPOUND 48 80-INDUCED CONJUNCTIVITIS IN THE MOUSE - KINETICS, SUSCEPTIBILITY, AND MECHANISM/

A mouse model of conjunctivitis has been developed by topical applicat ion of compound 48/80 (C48/80), an agent that triggers mast cell degra nulation. We examined the responsiveness of C57BL/6, C3H/HeN, and ASW/ J mouse strains to C48/80 stimulation, and of a mutant strain with mas t cell depletion (WBB6F1/J and its sham control). Conjunctivae were co llected and examined histopathologically at 15 min and 1,6,24,48, and 72 h after topical C48/80 administration. Conjunctival inflammation de veloped in all strains, although the severity varied. The conjunctivit is was characterized clinically by irritation, discharge, erythema, an d chemosis. Pathology showed conjunctival infiltration with neutrophil s, macrophages, CD4+ T lymphocytes, and a few eosinophils. Degranulati on of mast cells and evacuation of goblet cells were also observed. La te-phase inflammatory reactions peaked 6-24 h after C48/80 administrat ion and resolved by 48-72 h. WBB6F1/J mice had much less inflammation than their sham controls. In conclusion, topical C48/80 induced a conj unctival inflammatory response similar to allergen-induced conjunctivi tis. The depletion of mast cells significantly reduced the inflammatio n. This model which consistently mimics the clinical signs and histopa thological processes of allergic conjunctivitis in humans, is practica l and reliable for the evaluation of new anti-allergic medications and for the investigation of conjunctival cellular responses in the aller gic inflammatory cascade.