Nona-D-Arginine Therapy for Pseudomonas aeruginosa Keratitis

PURPOSE. Nona-D-arginine amide (D9R) was evaluated as treatment for Pseudomonas aeruginosa keratitis when administered alone and with ciprofloxacin. METHODS. Mouse corneas were infected with P. aeruginosa. Immediately after infection and hourly for 5 hours, eyes received 5 mu L of either Dulbecco phosphate-buffered saline (DPBS), 10 mu M D9R, or 100 mu M D9R. At 16 hours postinfection (PI) and then hourly for 5 hours, eyes treated with D9R or D-PBS then received 5 mu L ciprofloxacin (0.08%) or deionized water. On days 1, 7, and 14 PI, eyes were scored on a scale of 0 (normal eye) to +4 (corneal perforation). On day 1 PI, mice were euthanatized and eyes were harvested for histopathology or colony-forming unit (CFU) determination. At 6, 12, and 24 hours PI, corneas treated with 100 mu M D9R or D-PBS alone were harvested for the determination of IL-1 beta cytokine concentrations. RESULTS. Eyes treated with 10 or 100 mu M D9R and ciprofloxacin had significantly less disease than eyes treated with D-PBS and ciprofloxacin. Fewer than 30 CFUs were recovered from any eye treated with ciprofloxacin. Eyes treated with D9R alone had significantly less disease and lower IL-1 beta cytokine concentrations than D-PBS-treated eyes; however, there were no significant differences in CFU (>= 4 log 10) between these groups. CONCLUSIONS. Administration of 10 or 100 mu M D9R effectively reduced the abnormality associated with P. aeruginosa keratitis. Treatment with D9R and ciprofloxacin was superior to treatment with antibiotic alone by reducing ocular disease through suppression of the proinflammatory cytokine IL-1 beta and eradicating viable bacteria from the eye. (Invest Ophthalmol Vis Sci. 2009; 50: 256-262) DOI: 10.1167/iovs.08-2344