title: b-FGF induces corneal blood and lymphatic vessel growth in a spatially distinct pattern.
abstract: OBJECTIVE
  To study the spatial variances in ligand expression and angiogenic effect in response to the inflammatory response induced by basic fibroblast growth factor (b-FGF).
  
  
  METHODS
  b-FGF micropellets (80 ng) were implanted in the temporal side of the cornea of Balb/c mice. On days 1, 3, and 7, blood (heme-) and lymphangiogenesis were observed by immunofluorescence staining of corneal flat mounts with LYVE-1 and CD31 to identify lymphatic and blood vessels, respectively. A second group of corneas were harvested for quantitative real-time polymerase chain reaction. Each cornea was divided into 2 different areas: (1) pre-pellet area and (2) opposite-pellet area. Expression of vascular endothelial growth factor (VEGF) ligands was evaluated using real-time polymerase chain reaction in each respective zone.
  
  
  RESULTS
  Blood vessels grew into the cornea from the pre-pellet area, whereas corneal lymphatic vessels grew from the opposite-pellet area toward the center of the cornea. VEGF-A was upregulated in the pre-pellet, whereas VEGF-D expression was mostly observed in the opposite-pellet area. VEGF-C level increased simultaneously in both areas.
  
  
  CONCLUSIONS
  A single inducing factor, that is, b-FGF, may simultaneously provoke hemangiogenesis and lymphangiogenesis in different locations of the cornea through differential expression of VEGF ligands. This distinctive spatial pattern should be considered while evaluating the corneal predilection for inflammation beyond that which is directly visible by slit lamp examination.
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.
authors.forename: Amir R
authors.initials: AR
authors.lastname: Hajrasouliha
authors.forename: Zahra
authors.initials: Z
authors.lastname: Sadrai
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Chauhan
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003315:Cornea / Q000098:blood supply*; D016510:Corneal Neovascularization / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D004343:Drug Implants; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D019084:Fluorescent Antibody Technique, Indirect; D006023:Glycoproteins / Q000378:metabolism; D008024:Ligands; D042583:Lymphangiogenesis / Q000187:drug effects*; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology*; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D015415:Biomarkers; D004343:Drug Implants; D016222:Fibroblast Growth Factor 2; D006023:Glycoproteins; D008024:Ligands; D026901:Membrane Transport Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C492273:LYVE1 protein, mouse; C467480:vascular endothelial growth factor A, mouse