In the first grant period we determined that the mast cells in and around the eye could participate in anaphylaxis. In the second period we developed and characterized several models of ocular anaphylaxis. We now propose to use our model of topically induced ocular anaphylaxis to study the modulation of the early and late phases of ocular anaphylaxis.
(Aim 1) We will develop a simpler, more economical topical model of anaphylaxis.
(Aim 2) For Zero Phase (premast cell activation phase) of ocular anaphylaxis, we will induce specific antibody of the IgG2a, IgA, or secretory IgA types to trap antigen as it progresses from the ocular surface to the ocular mast cells.
(Aim 3) We will examine a method for testing modulation by topical application of drug in the model of topically induced ocular anaphylaxis, using corticosteroids as the prototype drug.
(Aim 4) We will modulate Phase I (mast cell degranulation and mediator phase) by mast cell-influencing drugs such as cromolyn and theophylline; by arachidonic acid metabolism inhibitors, diethylcarbamazine and aspirin; and by H1 and H2 blockers and vasoconstrictors.
(Aim 5) We will modulate Phase II (granulocyte part of the late phase) by inhibiting neutrophil accumulation with systemic and local vinblastine and anti-neutrophil antiserum. (6) We will modulate Phase III (mononuclear part of the late phase) by attempts at decreasing macrophage accumulation (by corticosteroid and phenylbutazone treatment) and, in other experiments, by increasing tissue macrophage accumulation by injecting foreign proteins into tissue. Ocular anaphylaxis will be analyzed by clinical evaluation with slit lamp, determination of antibody content of serum, tears, and tissue by the ELISA technique and radioimmunoassay, detection and location of specific antibody and antibody-forming cells by the fluorescent antibody technique, and quantitation of inflammatory ocular tissue infiltrates by counting cells on glutaraldehyde-fixed, 1-Mum sections stained with alkaline Giemsa. This program should provide information on the modulation of the many phases of ocular anaphylaxis. Once a better understanding of these phases and their relationship to ocular injury is appreciated, consideration of treatment programs for human diseases will be placed on a more scientific and possibly more effective basis.
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