The Induction of Anterior Chamber Inflammation by Factors Released from Hydrogen Peroxide-Injured Corneas: Effect of Dexamethasone and Indomethacin

ABSTRACT

Studies from our laboratory have demonstrated the release of high levels of neutrophil chemotactic factors (NCF) from isolated rabbit corneas injured by hydrogen peroxide (H₂0₂). 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 induce 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) (lmg/ml) and glucose oxidase (GO) (20 U/ml) at 37°C for 6 hours. This supernatant solution was collected and a 100 ul sample containing NCF, but not H₂0₂, was injected into the anterior chamber of anesthetized rabbit eyes (n = 8). Anterior chamber inflammation, characterized by moderate corneal edema associated with a fibrinous anterior chamber reaction, was evident 2 and 4 hours after injection. Aqueous humor analysis revealed the presence of fibrin and a large number of neutrophils (32 ± 5 × 10⁴ cells/ml). Control eyes, on the other hand, showed normal morphology and low levels of neutrophils after the injection of 100 ul minimum essential medium (MEM) (n = 8) (1.2 ± 0.14 × 10⁴ cells/ml), G/GO mixture (n = 8) (5 ± 0.86 × 10⁴ cells/ml), or supernatant solutions collected from MEM-treated corneas (n = 8) (15 ± 2 × 10⁴ cells/ml). To determine whether the inflammatory reaction observed was due to a direct effect of the chemoattractants or mediated through stimulation of arachidonic acid (AA) metabolites, we pretreated rabbit eyes with a sterile solution 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 to 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 reaction was observed with or without prior treatment with AA metabolite inhibitors. No difference in the degree of inflammation was detected clinically. Results of these studies suggest that NCF released from H₂0₂-injured corneas can directly induce inflammation of the anterior segment, and that metabolites of AA are not mediating the observed in vivo response.