One of the main causes of microbial keratitis is the improper use of soft contact lenses (CLs). This is because CLs can be colonized and infected by different types of microorganisms, such as Pseudomonas aeruginosa or Staphylococcus aureus. These pathogens are opportunistic microorganisms that are able to directly damage the corneal tissue leading to its perforation. They can adhere to the CLs surface forming biofilms. In additions, they have the ability to easily develop resistance to conventional antibiotics, making treatment of the infection often useless. In this scenario, new compounds capable of eradicating microbial infections, but also new strategies able to reduce lens colonization are highly necessary. Thanks to their interesting biological properties, antimicrobial peptides (AMPs) have attracted the attention of scientific research as candidates for the development of new antibacterial compounds. This is due to their membrane-perturbing mechanism of action that very rarely leads to resistance. AMPs have recently been characterized not only by their antibacterial properties, but also by a series of immunomodulatory functions. It has recently been demonstrated that two derivatives of the frog-skin esculentin-1a, named Esc(1-21) and Esc(1-21)-1c, have a potent anti-pseudomonal activity with immunomodulatory properties. Furthermore, Esc(1-21) was found to cause significant bacterial clearance in mouse models of keratitis. Another class of AMPs includes temporins, e.g. TA and TB, active especially against Gram-positive bacteria. These peptides are able to stimulate migration of keratinocytes and to kill intracellular S. aureus. Nevertheless, a relevant aim that needs to be achieved for the usage of AMPs in therapy includes the increase of their half-life and reduction in cytotoxicity. A promising strategy to reach these goals is given by peptides immobilization on CLs. The project will mainly focus on the biological characterization of peptide-coated CLs.
This project aims to further characterize the biological properties of antimicrobial peptides, as part of a well-known awareness campaign against the misuse of antibiotics. The onset of resistant infections is a global problem that has preoccupied the scientific community for years. More specifically, vision-threatening infections, e.g. keratitis, mainly due to contact-lens wear, cause vision loss yearly of about 200,000 people worldwide. It is therefore necessary to discover new compounds capable of not only eradicating infections but also preventing them. Moreover, the ease with which contact lenses are purchased for cosmetic purposes, even online, has led to the onset of increasingly frequent infections caused by improper use of the latter.
The powerful antibacterial action shown by AMPs, together with their immunomodulatory functions, make these compounds valid candidates for the development of ophthalmic formulations to combat microbial keratitis. Since bacterial adhesion to CLs is an essential step in the development of microbial keratitis, creating a surface able to inhibit the colonization of the lens by the microorganism could be a winning strategy to reduce the onset of infections. The conjugation of the peptides to contact lenses could represent an innovation in the biomedical field, either to limit the colonization of the lens or as a form of vehiculation of an anti-infective compound directly into the corneal tissue.