THE INDUCTION OF ANTERIOR-CHAMBER INFLAMMATION BY FACTORS RELEASED FROM HYDROGEN PEROXIDE-INJURED CORNEAS - EFFECT OF DEXAMETHASONE AND INDOMETHACIN

Studies from our laboratory have demonstrated the release of high leve ls of neutrophil chemotactic factors (NCF) from isolated rabbit cornea s injured by hydrogen peroxide (H2O2) The purpose of the present study was to determine the biological activity of these factors and to test the hypothesis that the intracameral injection of these factors can i nduce inflammation of the anterior segment. Under sterile conditions, the epithelial surfaces of isolated rabbit corneas were incubated with a 300 ul mixture of glucose (G) (1mg/ml) and glucose oxidase (GO) (20 U/ml) at 37 degrees C for 6 hours. This supernatant solution was coll ected and a 100 ul sample containing NCF, but not H2O2, was injected i nto the anterior chamber of anesthetized rabbit eyes (n = 8). Anterior chamber inflammation, characterized by moderate corneal edema associa ted with a fibrinous anterior chamber reaction, was evident 2 and 4 ho urs after injection. Aqueous humor analysis revealed the presence of f ibrin and a large number of neutrophils (32 +/- 5 x 10(4) cells/ml). C ontrol eyes, on the other hand, showed normal morphology and low level s of neutrophils after the injection of 100 ul minimum essential mediu m (MEM) (n = 8) (1.2 +/- 0.14 x 10(4) cells/ml), G/GO mixture (n = 8) (5 +/- 0.86 x 10(4) cells/ml), or supernatant solutions collected from MEM-treated corneas (n = 8) (15 +/- 2 x 10(4) cells/ml). To determine whether the inflammatory reaction observed was due to a direct effect of the chemoattractants or mediated through stimulation of arachidoni c acid (AA) metabolites, we pretreated rabbit eyes with a sterile solu tion of 0.1% dexamethasone (n = 8 eyes) or with a sterile solution of 3.4% indomethacin (n = 8 eyes) three times a day, for one day, prior t o the injection of NCF supernatant solution. Examination 2 hours and 4 hours after injection revealed inflammation characterized by mild-to- moderate corneal edema associated with a fibrinous anterior chamber re action was observed with or without prior treatment with BA metabolite inhibitors. No difference in the degree of inflammation was detected clinically. Results of these studies suggest that NCF released from H2 O2-injured corneas can directly induce inflammation of the anterior se gment, and that metabolites of AA are not mediating the observed in vi vo response.