Nona-D-Arginine Amide for Prophylaxis and Treatment of Experimental Pseudomonas aeruginosa Keratitis

Abstract

Purpose: 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.

Materials and Methods: Right eyes of Swiss Black mice received a 5 μl drop of either phosphate buffered saline (PBS, pH 7.4) or100 μM D9R every half-hour or hourly for 5 hr (total of 6–12 drops/eye) immediately after corneal wounding and subsequent infection with 1 × 10⁶ 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).

Results: P. aeruginosa-infected eyes treated with prophylactic D9R or with D9R after infection had significantly less ocular pathology (P ≤ 0.001) and bacterial burden (P ≤ 0.01) than eyes treated with PBS.

Conclusions: D9R (100 μM) 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.

KEYWORDS::

• Cornea
• Keratitis
• Nona-D-arginine
• Pseudomonas
• Therapy

ACKNOWLEDGMENTS

This research was supported through a donation made to The Foundation for the Louisiana State University Health Sciences Center in New Orleans.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.