The long-term goal of the five-year training program proposed in this application is to prepare the candidate, Ellen J. Lee, for an independent career in basic eye research studying the pathogenesis of ocular inflammation. Didactic activities including graduate level course work and seminars are proposed to supplement Dr. Lee's previous clinical optometry and graduate training with advanced training in the basic science discipline of immunology. The research component of this application, while will be conducted in Dr. Rosenbaum's laboratory using state-of-the-art methodologies, will involve studies of dendritic cells (DCs), macrophages, and polymorphonuclear leukocytes (PMNs) in the corneal inflammatory response to endotoxin exposure. The focus will be on characterizing the movement of these cells within the cornea, and investigating the role of cytokines and adhesion molecules that mediate their movement. Specifically, we will test the hypothesis that DCs, macrophages, and PMNs move in a linear and time-dependent fashion, but DC and macrophage movement is bidirectional, while PMN movement is unidirectional. We will also test the hypothesis that IL-1, TNF, MCP-1, and fractalkine, but not IL-6, will affect the migration of these cells within the cornea. Further, we hypothesize that the adhesion molecules beta1-integrin, CD47, discoidin domain receptor 1, tenascin, and CD44 play a major role in the movement of PMNs in the corneal stroma. These studies will be an important contribution to the understanding of the corneal inflammatory process, which may lead to the development of novet strategies for its prevention and/or control.
| Lee, Ellen J; Rosenbaum, James T; Planck, Stephen R (2010) Epifluorescence intravital microscopy of murine corneal dendritic cells. Invest Ophthalmol Vis Sci 51:2101-8 |
| Spencer, Doran B; Lee, Ellen J; Kawaguchi, Tatsushi et al. (2008) In vivo imaging of the immune response in the eye. Semin Immunopathol 30:179-90 |
