title: FasL-Fas interactions regulate neovascularization in the cornea.
abstract: OBJECTIVE
  Neovascularization of the avascular cornea is a significant problem associated with many corneal diseases. Because Fas ligand (FasL) is highly expressed in the cornea, the role of this molecule in controlling corneal neovascularization was examined in this study.
  
  
  METHODS
  C57BL/6(B6), FasL (CD95L)-deficient B6-gld, and Fas (CD95)-deficient B6-lpr mice were subjected to the suture model of neovascularization. Corneas were evaluated for neovascularization and representative samples subjected to immunohistochemical analysis for expression of Fas antigen and CD31 (platelet-endothelial cell adhesion molecule [PECAM-1]) on vessels that were present in the tissue. Corneas were also explanted and placed in collagen gel cultures to test the ability of anti-Fas antibody to prevent vessel extension from explanted corneas.
  
  
  RESULTS
  Immunohistochemical data demonstrated that quiescent vessels express CD31 alone, whereas vessels that penetrate the cornea coexpressed both the Fas antigen and CD31. A significant increase was observed in neovascularization in FasL-deficient B6-gld corneas compared with B6 corneas, and new vessel growth in both B6 and B6-gld was inhibited by anti-Fas antibody. Whereas Fas-deficient B6-lpr corneas displayed significantly less neovascularization than normal B6, B6-lpr mice express Fas on growing vessels. In corneal explant cultures, vessel growth from B6 and lpr mice corneas was inhibited by anti-Fas antibody, confirming functional Fas expression in B6-lpr mice.
  
  
  CONCLUSIONS
  These data indicate that FasL is an important factor in controlling corneal neovascularization.
authors.affiliation: Departments of Ophthalmology and Visual Sciences, Washington University Medical School, 660 S. Euclid Avenue, St. Louis, MO 63110, USA. stuart@vision.wustl.edu
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Stuart
authors.forename: Fan
authors.initials: F
authors.lastname: Pan
authors.forename: Stacey
authors.initials: S
authors.lastname: Plambeck
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Ferguson
mesh_terms: D000818:Animals; D003315:Cornea / Q000098:blood supply / Q000378:metabolism; D016510:Corneal Neovascularization / Q000378:metabolism* / Q000473:pathology; D053222:Fas Ligand Protein; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019014:fas Receptor