LECITHIN-BOUND SUPEROXIDE-DISMUTASE IN THE PREVENTION OF NEUTROPHIL-INDUCED DAMAGE OF CORNEAL TISSUE

PURPOSE. To evaluate the effects of a lipophilic analog of superoxide dismutase (SOD) in the prevention of polymorphonuclear leukocyte (PMN) -induced damage to corneal epithelial cells in vitro and in bacterial corneal ulcers in vivo. METHODS. Immortalized human corneal epithelial cells (T-HCEC) were cocultured with human PMNS activated with N-formy l-methionyl-leucyl-phenylalanine for 18 hours, after which lactate deh ydrogenase (LDH) activity of the supernatant was measured as a marker of cellular damage. The inhibitory effects of lecithin-bound SOD (PC-S OD) and unmodified SOD, as well as PMNs pretreated with anti-CD 18 mon oclonal antibody, were compared with untreated control. The retention of each drug on the ocular surface of healthy volunteers was measured by now cytometry using brush cytology samples. The protective effects of a 0.1% solution of PC-SOD on Pseudomonas aeruginosa corneal infecti on in guinea pigs were assessed by inflammatory grading scores and his tology. RESULTS. Both PC-SOD and SOD effectively suppressed PMN-induce d LDH release in T-HCEC in a dose-dependent manner. LDH release was al so attenuated when PMNs were pretreated with anti-CD 18 antibodies, su ggesting that adhesion molecules were involved in the process. Brush c ytology of conjunctival samples showed that PC-SOD was retained longer on the ocular surface compared with unmodified SOD. PC-SOD significan tly prevented excessive tissue damage by infiltrating PMNs in P. aerug inosa corneal infection, whereas in control eyes, perforation of the c ornea occurred by 6 days. CONCLUSIONS. PC-SOD was effective in attenua ting PMN-related tissue damage to corneal tissue both in vitro and in P. aeruginosa infection in guinea pigs.