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Nona-D-arginine therapy for Pseudomonas aeruginosa keratitis
Priyanka Karicherla1, Jeffery A Hobden
1Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
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 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.
Results:
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.
Conclusions:
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.
Insights
Nona-D-arginine amide (D9R) effectively treated Pseudomonas aeruginosa keratitis, reducing ocular disease and inflammation. When combined with ciprofloxacin, D9R eradicated bacteria and offered superior therapeutic benefits.
Area of Science:
- Ophthalmology
- Microbiology
- Immunology
Background:
- Pseudomonas aeruginosa keratitis is a severe ocular infection.
- Effective antimicrobial and anti-inflammatory treatments are crucial for managing this condition.
Purpose of the Study:
- To evaluate nona-D-arginine amide (D9R) as a treatment for Pseudomonas aeruginosa keratitis.
- To assess the efficacy of D9R alone and in combination with ciprofloxacin.
Main Methods:
- Mouse corneas were infected with P. aeruginosa.
- Eyes were treated with D9R, ciprofloxacin, or combinations thereof.
- Ocular disease, bacterial load (CFU), and IL-1beta levels were assessed.
Main Results:
- D9R alone and with ciprofloxacin significantly reduced keratitis severity.
- Combined D9R and ciprofloxacin treatment eradicated viable bacteria.
- D9R treatment lowered IL-1beta cytokine concentrations.
Conclusions:
- Nona-D-arginine amide (D9R) is an effective treatment for P. aeruginosa keratitis.
- Combination therapy with D9R and ciprofloxacin demonstrates superior efficacy.
- D9R reduces ocular disease by suppressing IL-1beta and eradicating bacteria.
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