Abstract
Bacterial keratitis is an ocular infection that can lead to severe visual disability. Staphylococcus aureus is a major pathogen of the eye. We recently demonstrated the strong antimicrobial activity of LyeTxI-b, a synthetic peptide derived from a Lycosa erithrognatha toxin. Herein, we evaluated a topical formulation (eye drops) containing LyeTxI-b to treat resistant bacterial keratitis. Keratitis was induced with intrastromal injection of 4 × 105 cells (4 µL) in New Zealand female white rabbits. Minimum inhibitory concentration (MIC) and biofilm viability were determined. LyeTxI-b ocular toxicity was evaluated through chorioallantoic membrane and Draize tests. One drop of the formulation (LyeTxI-b 28.9 µmol/L +0.5% CMC in 0.9% NaCl) was instilled into each eye four times a day, for a week. Slit-lamp biomicroscopy analysis, corneal histopathological studies and cellular infiltrate quantification through myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) detection were performed. LyeTxI-b was very effective in the treatment of keratitis, with no signs of ocular toxicity. Planktonic bacteria MIC was 3.6 µmol/L and LyeTxI-b treatment reduced biofilm viability in 90%. LyeTxI-b eliminated bacteria and reduced inflammatory cellular activity in the eyes. Healthy and treated animals showed similar NAG and MPO levels. LyeTxI-b is a potent new drug to treat resistant bacterial keratitis, showing effective antimicrobial and anti-inflammatory activity.
Highlights
The eye is relatively resistant to microorganisms and most pathogens cannot cross the intact cornea, because the eye provides a diverse collection of antimicrobial factors, especially in the tear film, which protects the cornea from infection [1]
Microbial keratitis is characterized by a defect in the corneal epithelium with stromal inflammation caused by microorganisms
Positive and negative controls were submitted to 24 h at 37 °C
Summary
The eye is relatively resistant to microorganisms and most pathogens cannot cross the intact cornea, because the eye provides a diverse collection of antimicrobial factors, especially in the tear film, which protects the cornea from infection [1]. If there is any structural damage or failure in the defense mechanisms that maintain its entire surface, opportunistic infections can develop, resulting in microbial keratitis [1,2,3]. Microbial keratitis is characterized by a defect in the corneal epithelium with stromal inflammation caused by microorganisms. Bacterial keratitis is considered one of the most serious ocular conditions in the world and may cause partial or total loss of visual acuity [4,5,6].
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