Ocular anaphylaxis induced in the rat by topical application of compound 48/80. Dose response and time course study

In the present study we sought to develop a model of ocular anaphylaxis based on the topical application of compound 48/80 to the surface of the rat eye. Doses ranging from 50 to 1000 micrograms were found to produce graded edema of the conjunctiva and swelling of the lid. On histologic examination, 50 microns compound 48/80 produced no changes distinguishable from those in PBS-treated controls, 150 microns produced mild alterations, and 250, 500, and 1000 micrograms compound 48/80 produced a marked increase in degranulated mast cells and a mild influx of neutrophils. The time course of the response to 250 micrograms and 1000 micrograms of compound 48/80 was evaluated over a 72-h period. Both doses elicited epithelial damage. A mild reduction in the number of mast cell was seen at 6 h in rats receiving 250 or 1000 micrograms. The reduction persisted to 72 h in rats receiving 1000 micrograms. The number of neutrophils was increased at 1 and 6 h in eyes treated with 250 micrograms and at 1, 6, and 24 h in eyes treated with 1000 micrograms compound 48/80. The clinical and histologic changes induced by application of 250 micrograms compound 48/80 resemble those seen in patients with allergic conjunctivitis suggesting that a model of ocular anaphylaxis based on the topical application compound 48/80 will be clinically relevant and experimentally practical.