Mechanisms of wound healing and disinfection in a plasma source for the treatment of corneal infections

Cold atmospheric pressure plasmas provide the potential for effective treatment of infectious keratitis, a sight-threatening process with a worldwide occurrence of 2 million cases/yr. In microbial keratitis, bacteria, fungi, viruses, or small eukaryotes penetrate and proliferate in the cornea, causing inflammation and tissue ulceration. The requirement of clinical approaches to overcome antibiotic resistance and simultaneously foster tissue healing prompted us to develop a plasma source generated by ionizing helium flow for ophthalmologic applications. Using plasma, we reported significant reductions in load of bacteria, virus, and fungi that are frequently involved in infectious keratitis. Plasma exposure induced formation of reactive oxygen and nitrogen species in human cells, accounting for the already described biological effects. Actually, nontoxic levels of reactive species elicit intracellular signals and modulate hypoxia-related gatekeeper transcriptional factors such as nuclear factor-?B and hypoxia-inducible factor-1?. Together, these data make cold atmospheric pressure plasma generated by ionizing helium flow a valid approach for the treatment of infectious keratitis.