nonaarginine and Corneal-Ulcer

Nona-D-arginine amide (D9R) affected a cure of Pseudomonas aeruginosa corneal disease when combined with ciprofloxacin. In this study, we show that D9R alone and prophylactic treatment with D9R significantly reduced corneal pathology and bacterial burden associated with P. aeruginosa infection.. Right eyes of Swiss Black mice received a 5 microl drop of either phosphate buffered saline (PBS, pH 7.4) or100 microM D9R every half-hour or hourly for 5 hr (total of 6-12 drops/eye) immediately after corneal wounding and subsequent infection with 1 x 10(6) colony forming units (CFU) of a cytotoxic strain of P. aeruginosa (ATCC 19660). For prophylactic treatment, eyes were treated hourly for 5 hr (total of 6 drops/eye) before infection with an invasive strain of P. aeruginosa (PAO1). At 24 hr post infection, all eyes were evaluated for pathology and scored on a scale of 0 (normal eye) to +4 (corneal perforation). Mice were then sacrificed and eyes were harvested for CFU determination (N = 15) or histopathology (N = 5).. P. aeruginosa-infected eyes treated with prophylactic D9R or with D9R after infection had significantly less ocular pathology (P < or = 0.001) and bacterial burden (P < or = 0.01) than eyes treated with PBS.. D9R (100 microM) would be a beneficial addition to current antimicrobial therapy for P. aeruginosa corneal disease. Furthermore, D9R can be incorporated into ophthalmic solutions as a prophylactic agent with the potential of reducing the incidence and severity of P. aeruginosa ocular infection.

Topics: Animals; Antibiotic Prophylaxis; Colony Count, Microbial; Cornea; Corneal Ulcer; Disease Models, Animal; Disease Progression; Eye Infections, Bacterial; Female; Furin; Male; Mice; Oligopeptides; Pseudomonas aeruginosa; Pseudomonas Infections

Nona-D-arginine amide (D9R) was evaluated as treatment for Pseudomonas aeruginosa keratitis when administered alone and with ciprofloxacin.. Mouse corneas were infected with P. aeruginosa. Immediately after infection and hourly for 5 hours, eyes received 5 microL of either Dulbecco phosphate-buffered saline (D-PBS), 10 microM D9R, or 100 microM D9R. At 16 hours postinfection (PI) and then hourly for 5 hours, eyes treated with D9R or D-PBS then received 5 microL 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 microM D9R or D-PBS alone were harvested for the determination of IL-1beta cytokine concentrations.. Eyes treated with 10 or 100 microM 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-1beta cytokine concentrations than D-PBS-treated eyes; however, there were no significant differences in CFU (> or = 4 log(10)) between these groups.. Administration of 10 or 100 microM 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-1beta and eradicating viable bacteria from the eye.

Topics: Animals; Ciprofloxacin; Colony Count, Microbial; Cornea; Corneal Ulcer; Disease Models, Animal; Drug Therapy, Combination; Eye Infections, Bacterial; Female; Furin; Interleukin-1beta; Mice; Oligopeptides; Pseudomonas aeruginosa; Pseudomonas Infections