Lecithin-bound superoxide dismutase in the prevention of neutrophil-induced damage of corneal tissue.
OBJECTIVE
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-formyl-methionyl-leucyl-phenylalanine for 18 hours, after which lactate dehydrogenase (LDH) activity of the supernatant was measured as a marker of cellular damage. The inhibitory effects of lecithin-bound SOD (PC-SOD) and unmodified SOD, as well as PMNs pretreated with anti-CD 18 monoclonal antibody, were compared with untreated control. The retention of each drug on the ocular surface of healthy volunteers was measured by flow cytometry using brush cytology samples. The protective effects of a 0.1% solution of PC-SOD on Pseudomonas aeruginosa corneal infection in guinea pigs were assessed by inflammatory grading scores and histology.


RESULTS
Both PC-SOD and SOD effectively suppressed PMN-induced LDH release in T-HCEC in a dose-dependent manner. LDH release was also attenuated when PMNs were pretreated with anti-CD 18 antibodies, suggesting that adhesion molecules were involved in the process. Brush cytology of conjunctival samples showed that PC-SOD was retained longer on the ocular surface compared with unmodified SOD. PC-SOD significantly prevented excessive tissue damage by infiltrating PMNs in P. aeruginosa corneal infection, whereas in control eyes, perforation of the cornea occurred by 6 days.


CONCLUSIONS
PC-SOD was effective in attenuating PMN-related tissue damage to corneal tissue both in vitro and in P. aeruginosa infection in guinea pigs.
Matsumoto
K
K
Department of Ophthalmology, Kumamoto University School of Medicine, Japan.
Shimmura
S
S
Goto
E
E
Saito
K
K
Takeuchi
T
T
Miyajima
S
S
Negi
A
A
Tsubota
K
K
D000818:Animals; D018821:CD18 Antigens / Q000276:immunology; D018929:Cell Culture Techniques; D002460:Cell Line; D018920:Coculture Techniques; D003315:Cornea / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D003320:Corneal Ulcer / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D015818:Eye Infections, Bacterial / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry; D006168:Guinea Pigs; D006801:Humans; D007634:Keratitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology*; D010713:Phosphatidylcholines / Q000378:metabolism / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology*
D018821:CD18 Antigens; D010713:Phosphatidylcholines; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase