Analysis of strain-dependent differences in corneal lymphangiogenesis for the identification of new endogenous regulators of lymphangiogenesis

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The cornea is physiologically avascular, i.e. free of blood and lymph vessels to ensure transparency and good vision. As a consequence of numerous diseases both vessel types can secondarily invade into the cornea, leading to loss of vision or blindness. In the context of corneal transplantation the ingrowths of lymphatics increases the risk for an immune response following transplantation. However, the molecular pathways concerning corneal alymphaticity and observed differences in the lymphangiogenic response due to inflammation are not completely understood. We previously could show that strain-dependent differences in lymphangiogenesis exist among mouse strains. As a next step the cornea of three phenotypically different mouse strains was compared with gene expression analysis, which revealed potential candidates involved in regulation of lymphangiogenesis. The objectives of this project therefore are 1. to analyze the impact of the identified candidates on modulation of lymphatic vascular endothelium, 2. to identify candidate genes for the strain-dependent differences using a positional cloning strategy and 3. to use this approach with the cornea as a model system to identify new endogenous regulators of lymphangiogenesis and get insight into the corneal lymphangiogenic privilege. New endogenous inhibitors of lymphangiogenesis could help improving graft survival and may also help to avoid lymphogenic metastatic tumor spread.