Novel Peptides with Dual Properties for Treating Pseudomonas aeruginosa Keratitis: Antibacterial and Corneal Wound Healing

Abstract

The corneal epithelium is a layer in the anterior part of eye that contributes to light refraction onto the retina and to the ocular immune defense. Although an intact corneal epithelium is an excellent barrier against microbial pathogens and injuries, corneal abrasions can lead to devastating eye infections. Among them, Pseudomonas aeruginosa-associated keratitis often results in severe deterioration of the corneal tissue and even blindness. Hence, the discovery of new drugs able not only to eradicate ocular infections, which are often resistant to antibiotics, but also to elicit corneal wound repair is highly demanded. Recently, we demonstrated the potent antipseudomonal activity of two peptides, Esc(1-21) and its diastereomer Esc(1-21)-1c. In this study, by means of a mouse model of P. aeruginosa keratitis and an in vivo corneal debridement wound, we discovered the efficacy of these peptides, particularly Esc(1-21)-1c, to cure keratitis and to promote corneal wound healing. This latter property was also supported by in vitro cell scratch and ELISA assays. Overall, the current study highlights Esc peptides as novel ophthalmic agents for treating corneal infection and injury, being able to display a dual function, antimicrobial and wound healing, rarely identified in a single peptide at the same micromolar concentration range.

A Systematic Review of the Design and Applications of Antimicrobial Peptides in Wound Healing

“…The synthetic AMP Esc(1-21) has 21 residues and is generated from Esculentin-1A, the parent AMP. Its diastereomer is Esc(1-21)-1c [ 60 ]. A unique synthetic AMP called HX-12C was created to hasten the healing of wounds [ 61 ].…”

“…Esc(1-21) and Esc(1-21)-1c were tested for their ability to promote wound healing using human corneal epithelial cells (HCECs) in an in vitro scratch assay [ 60 ]. The data revealed that both peptides helped close the gap area in a way that was dependent on time and dose.…”

“…The data revealed that both peptides helped close the gap area in a way that was dependent on time and dose. Esc(1-21) treatment produced significantly decreased scratch areas at 20 μM [ 60 ]. Furthermore, the investigation discovered that, rather than cell proliferation, cell migration is mostly responsible for the wound-healing activity caused by Esc peptides [ 60 ].…”

“…Esc(1-21) treatment produced significantly decreased scratch areas at 20 μM [ 60 ]. Furthermore, the investigation discovered that, rather than cell proliferation, cell migration is mostly responsible for the wound-healing activity caused by Esc peptides [ 60 ]. According to the measurement of the circularity index, the results demonstrated that Esc(1-21)-1c considerably enhanced corneal smoothness, suggesting that it may have the ability to promote wound healing [ 60 ].…”

“…Furthermore, the investigation discovered that, rather than cell proliferation, cell migration is mostly responsible for the wound-healing activity caused by Esc peptides [ 60 ]. According to the measurement of the circularity index, the results demonstrated that Esc(1-21)-1c considerably enhanced corneal smoothness, suggesting that it may have the ability to promote wound healing [ 60 ]. The effectiveness of Esc(1-21)-1c in encouraging wound healing was further supported by the fluorescein staining results in mice, which showed that at certain doses, it considerably decreased the corneal epithelial wound area [ 60 ].…”