June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Efficacy of a 10-amino-acid keratin-derived antimicrobial peptide (KAMP-10) against amikacin-resistant Pseudomonas aeruginosa keratitis in mice
Author Affiliations & Notes
  • Karthikeyan Bose
    Department of Ophthalmic Research, Cleveland Clinic Cole Eye Institute and Lerner Research Institute, Cleveland, Ohio, United States
  • K P Connie Tam
    Department of Ophthalmic Research, Cleveland Clinic Cole Eye Institute and Lerner Research Institute, Cleveland, Ohio, United States
    Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, United States
  • Footnotes
    Commercial Relationships   Karthikeyan Bose, None; K P Connie Tam, US Patent No. 9,187,541 B2 - “Anti-Microbial Peptides and Methods of Use Thereof” (P)
  • Footnotes
    Support  NIH-NEI R01EY023000 and Cleveland Clinic Seed Fund (K. P. C. Tam),NIH-NEI P30 Core Grant (IP30EY025585-01A1) and Unrestricted Grant from The Research to Prevent Blindness, Inc. (Cole Eye Institute).
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5769. doi:
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    • Get Citation

      Karthikeyan Bose, K P Connie Tam; Efficacy of a 10-amino-acid keratin-derived antimicrobial peptide (KAMP-10) against amikacin-resistant Pseudomonas aeruginosa keratitis in mice. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5769.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Keratin-derived antimicrobial peptides (KAMPs) are naturally produced by human corneal epithelial cells. Synthetic analogs of KAMPs have potent antibacterial and cytoprotective activity. Recently we reported the novel non-αβ structure of KAMPs and that the central 10-amino-acid hydrophobic strip (KAMP-10) is critical for bacterial membrane permeation. Here, we investigated the efficacy of exogenously administered synthetic KAMP-10 against amikacin-resistant P. aeruginosa keratitis in a mouse model.

Methods : Corneas of anesthetized C57BL/6 mice were scratched and allowed to heal for 4 h before inoculation of 104 CFU (in 5 μl saline) amikacin-resistant P. aeruginosa clinical isolate. KAMP-10 (200 ng) was topically applied once at the time of inoculation as prophylactic treatment. In other experiments, KAMP-10 was subconjunctivally injected (19.2 μg in 8 μl saline, once daily,) and topically applied (5 μg in 5 μl saline, four times daily) for 3 days beginning at 24 h post infection as therapeutic treatment. Vehicle-treated mice served as controls. Cornea pathology was scored daily (0-16 points). At the time of sacrifice, enucleated eyes were homogenized in 1 ml PBS to quantify viable bacteria load. Non-parametric Mann-Whitney U test was used for statistical comparison between two groups.

Results : Control eyes without prophylactic treatment had median [upper, lower quartile] disease scores of 8.5 [10.75, 6.25] and 10.5 [13, 9] at 24 h and 48 h post infection respectively, and bacterial load of 6.6x104 [8.1x104, 3.7x104] CFU/eye. In contrast, eyes treated with KAMP-10 prophylactically were uninfected (P < 0.0005 in each case). Eyes treated therapeutically also had significant reduction in disease scores (2 [3, 2] vs. 8 [8.75, 4.75] at 24 h post treatment) and bacterial load (0 [0, 0] vs. 1.6x104 [2.55x104, 1.05x104] CFU/eye) compared to untreated control (P < 0.001 in each case).

Conclusions : KAMP-10 treatment given prophylactically or therapeutically can effectively prevent or ameliorate P. aeruginosa-induced corneal infection in mice. The data suggest that KAMPs may serve as new treatment options or supplements to curb antibiotic-resistant corneal infection.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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