The laboratory’s long standing NIH (NEI) grant is aimed at understanding the molecular factors that prevent bacterial penetration of the corneal epithelium when the eye is healthy, how the functionality of that defense system is modulated, and the bacterial factors that enable penetration when the system is compromised. Barriers to our understanding in this area have included the lack of available in vivo models for studying these processes. Traditionally researchers have used “infection models” to study tissue interactions with bacteria. These involve deliberately compromising the tissue to induce enable susceptibility to infection, adding the microbe and then studying what happens next. Those who study corneal infection extensively use a scratch injury model that enables susceptibility by physically removing the epithelial barrier to expose the vulnerable stroma. Disease follows because direct placement of the microbe into the stroma stimulates a damaging inflammatory response.

This scratch injury model is problematic for the Fleiszig laboratory’s research goals for two reasons. Firstly, it bypasses the need for bacteria to penetrate the epithelium, which is the event the laboratory seeks to understand. Secondly, the lab is interested in understanding the events that determine health when the cornea is resistant to infection, not events that occur when there is disease. Due to the lack of suitable model systems, most of our knowledge about epithelial interactions with bacteria and the potential role of the epithelia in defense have necessarily come from cell culture studies.

In the past, the laboratory has succeeded in developing multiple models (in vivo and in vitro) that enable epithelial cell penetration by bacteria to be studied. Together, these models provide the opportunity to do experiments either in the context of, or without, potentially confounding factors present in vivo, as is needed to test hypotheses. In the past year, the laboratory has also developed new imaging technologies that enable bacterial interactions with the epithelium to be imaged in living intact eyes without the need for any tissue dissection, staining, or other types of sample preparation/processing.