title: The Naïve Murine Cornea as a Model System to Identify Novel Endogenous Regulators of Lymphangiogenesis: TRAIL and rtPA.
abstract: BACKGROUND
  In the murine cornea, which is an established model for analyzing pathologic lymphatic vessel growth, phenotypic heterogeneity of the endogenous lymphatic vessels in the limbus of the cornea was previously described. In this study, the cornea of BALB/c, C57BL/6, and FVB mice with different limbal lymphangiogenic phenotypes was analyzed to identify novel candidates potentially influencing lymphatic vessel growth.
  
  
  RESULTS
  Pathway specific expression analysis of the cornea was performed to identify novel candidate genes. Corneal protein expression of the respective candidates was analyzed by fluorescent immunohistochemistry. The effect of the candidates on proliferation of human dermal lymphatic endothelial cells (HDLECs) was analyzed by BrdU proliferation ELISA. Thirteen genes were differentially regulated in corneas of mouse strains with more endogenous limbal lymphatic vessels (high-lymphangiogenic) (C57BL/6) compared to mouse strains with less endogenous limbal lymphatic vessels (low-lymphangiogenic) (BALB/c, FVB). Two candidates, Tumor necrosis factor (ligand) superfamily member 10 (Tnfsf10/Trail) and Plasminogen activator, tissue (Plat/tPA) were expressed in the cornea of BALB/c and C57BL/6 mice on the protein level. In vitro, Trail and recombinant tPA inhibited the proliferation of human dermal lymphatic endothelial cells.
  
  
  CONCLUSIONS
  Molecular analysis of the naive cornea in mouse strains with different limbal lymphatic phenotypes is a valuable model to identify novel endogenous regulators of lymphangiogenesis.
authors.affiliation: 1 Department of Ophthalmology, University of Cologne , Germany .
authors.forename: Birgit
authors.initials: B
authors.lastname: Regenfuß
authors.affiliation: 1 Department of Ophthalmology, University of Cologne , Germany .
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Dreisow
authors.affiliation: 1 Department of Ophthalmology, University of Cologne , Germany .
authors.forename: Deniz
authors.initials: D
authors.lastname: Hos
authors.affiliation: 2 Department of Ophthalmology, Boston University School of Medicine , Boston, Massachusetts.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Masli
authors.affiliation: 1 Department of Ophthalmology, University of Cologne , Germany .
authors.forename: Felix
authors.initials: F
authors.lastname: Bock
authors.affiliation: 1 Department of Ophthalmology, University of Cologne , Germany .
authors.forename: Claus
authors.initials: C
authors.lastname: Cursiefen
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003315:Cornea / Q000187:drug effects / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D042583:Lymphangiogenesis / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000378:metabolism / Q000494:pharmacology
chemical_list: D053221:TNF-Related Apoptosis-Inducing Ligand; D010959:Tissue Plasminogen Activator