In vitro model of the closed eye environment and material-induced inflammation

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Inflammation is an integral part of the cell response to biomedical devices, such as contact lens, stent and vascular graft. Despite many years of research, we have yet to design materials that are able to interact with the human body without causing complications. To design materials that are compatible with human biological systems, one must first understand how cells interact with materials. Furthermore, appropriate experimental models are needed to test the cell response in an environment that appropriately mimics the biological system of study. Because the eye is a difficult environment to model, little research has been done in this area. This is especially true for neutrophils, inflammatory white blood cells, which invade the front of the eye during prolonged eye closure (3 hours or more). These neutrophils, due to their nature as inflammatory cells, have the potential to create significant damage as they possess an arsenal of inflammatory compounds aimed at fighting off infection and foreign materials. However, while they can be found in the hundreds of thousands in the closed-eye environment, they appear to have a limited ability to react and respond to normal inflammatory stimulus. Is the behavior of these cells due to their interactions with other cells or due to the presence of specific compounds in the tears? Using a mechanistic in vitro approach, this research grant proposal aims to gain a better understanding of the cellular mechanisms involved. Using various cell culture conditions, neutrophils will be incubated with different proteins known to be present in tears and will be allowed to interact with corneal and conjunctival cells. The role that specific proteins, inflammatory compounds and cells play in the neutrophil’s ability to respond to inflammatory stimulus in an environment that mimics the front of the eye will be determined. These experiments will not only enable us to develop a true in vitro model of the closed-eye environment but will also enable us to characterize the inflammatory cell response. Furthermore, using this in vitro model, we will determine the effect that a foreign material such as a contact lens has on the neutrophil inflammatory response. Ultimately, this research program will create new knowledge on the cellular mechanisms of inflammation in the ocular environment, but also on how these can relate to the inflammatory response induced by the presence of a biomaterial. All together, this research program will help identify key molecular pathways that will represent novel research strategies for manufacturers to develop better pharmaceuticals and materials that are more compatible with the eye. This program will train four graduate students in interdisciplinary research using methodology related to cell biology, in vitro models and interaction with materials. The expertise the students will gain will allow them to join the rapidly emerging and critically important Canadian biomedical and biotechnology industry.