Effect of multiple applications of compound 48/80 on mast cells of rat conjunctiva

We sought to determine the effect on rat conjunctival mast cells of chronic exposure to a degranulating agent. Compound 48/80 (250 micrograms in 10 microliter) was applied daily to the ocular surface of rats for a total of 13 treatments administered in 17 days. A single application of compound 48/80 was given to rats for comparison. Four groups of animals (6 in each group) were evaluated 1 or 48 h after the last application of compound 48/80 in both chronic exposure and single exposure studies. Although a single exposure to compound 48/80 induced significant degranulation of mast cells in animals observed 1 h after treatment, no significant degranulation of mast cells was observed 1 h after the last dose of compound 48/80 was given to rats whose conjunctiva had been chronically exposed to this degranulating agent. Thus, multiple applications of compound 48/80 attenuated the mast cell response to compound 48/80. This acquired tolerance to compound 48/80 was reflected in the lessened clinical signs in rats receiving repeated applications compared with those given a single application.