title: Blockade of the VEGF isoforms in inflammatory corneal hemangiogenesis and lymphangiogenesis.
abstract: BACKGROUND
  The VEGF-A family plays a crucial role in the induction of pathological corneal neovascularization. The role of the different VEGF-A isoforms during lymphangiogenesis is only little-known. Current anti-angiogenic therapies in the eye and other organs inhibit all VEGF-A isoforms, and have effects on both blood and lymphatic vessels. Here we investigate whether selective targeting of the isoform VEGF 165 is able to inhibit corneal lymphangiogenesis under inflammatory conditions.
  
  
  METHODS
  The mouse model of suture-induced corneal neovascularization was used to assess the antihem- and antilymphangiogenic effect of topically applied pegaptanib. Corneal blood and lymph vascularized areas were analyzed morphometrically. Furthermore, we analyzed the proliferative effects of VEGF A 121, 165, and 189 on blood and lymphatic endothelial cells (BEC/LEC) via a cell-proliferation assay.
  
  
  RESULTS
  Pegaptanib significantly inhibited inflammatory corneal hemangiogenesis (p < 0.01), but not lymphangiogenesis in vivo (p > 0.05), both topically as well as systemically, in the inflamed cornea. In vitro, BECs were more susceptible to pegaptanib than LECs.
  
  
  CONCLUSIONS
  Targeting VEGF-A 165 significantly inhibits hem- but not lymphangiogenesis, suggesting VEGF-A 165 to be critical for hem-, but dispensable for lymphangiogenesis, at least in the inflamed cornea.
authors.affiliation: Department of Ophthalmology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054, Erlangen, Bavaria, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Lipp
authors.forename: Franziska
authors.initials: F
authors.lastname: Bucher
authors.forename: Anand
authors.initials: A
authors.lastname: Parthasarathy
authors.forename: Deniz
authors.initials: D
authors.lastname: Hos
authors.forename: Jasmine
authors.initials: J
authors.lastname: Onderka
authors.forename: Claus
authors.initials: C
authors.lastname: Cursiefen
authors.forename: Felix
authors.initials: F
authors.lastname: Bock
mesh_terms: D000287:Administration, Topical; D000818:Animals; D052157:Aptamers, Nucleotide / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D016510:Corneal Neovascularization / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006023:Glycoproteins / Q000378:metabolism; D042583:Lymphangiogenesis / Q000502:physiology*; D026901:Membrane Transport Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009883:Ophthalmic Solutions; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D052157:Aptamers, Nucleotide; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D009883:Ophthalmic Solutions; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; C492273:LYVE1 protein, mouse; C467480:vascular endothelial growth factor A, mouse; C495058:pegaptanib
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