Nona-D-Arginine Therapy for Pseudomonas aeruginosa Keratitis

¹ Dept. of Microbiology, Immunology & Parasitology, LSU Health Sciences Center, New Orleans, Louisiana, United States

^* To whom correspondence should be addressed. E-mail: jhobde{at}lsuhsc.edu.

	Abstract

Purpose:Nona-D-arginine amide (D9R) was evaluated as treatment for P. 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 µl of either Dulbecco’s phosphate buffered saline (D-PBS), 10 µM D9R or100 µM D9R. At 16 hours post infection (PI) and then hourly for 5 hours, eyes treated with D9R or D-PBS then received 5 µl of ciprofloxacin (0.08%) or de-ionized 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 euthanized and eyes harvested for histopathology or CFU determination. At 6, 12 and 24 hours PI, corneas treated with 100 µM D9R or D-PBS alone were harvested for determining IL-1 cytokine concentrations. Results: Eyes treated with 10 or 100 µM D9R and ciprofloxacin had significantly less pathology than eyes treated with D-PBS and ciprofloxacin. Less than 30 CFU were recovered from any eye treated with ciprofloxacin. Eyes treated with D9R alone had significantly less pathology and lower IL-1 cytokine concentrations than D-PBS-treated eyes; however there were no significant differences in CFU (4 log₁₀) between these groups. Conclusion: Administration of 10 or 100 µM D9R effectively reduced the pathology associated with P. aeruginosa keratitis. Treatment with D9R and ciprofloxacin was superior to treatment with antibiotic alone by reducing ocular pathology through suppression of the pro-inflammatory cytokine IL-1 as well as eradicating viable bacteria from the eye.

Key Words: antibiotics, anti-inflammatory agents, pseudomonas keratitis, corneal ulceration, immunopathology