title: Regulation of blood vessel versus lymphatic vessel growth in the cornea.
abstract: OBJECTIVE
  In the present study, the authors developed novel models to stimulate blood vessel formation (hemangiogenesis) versus lymphatic vessel formation (lymphangiogenesis) in the cornea.
  
  
  METHODS
  Micropellets loaded with high-dose (80 ng) or low-dose (12.5 ng) basic fibroblast growth factor (bFGF) were placed in BALB/c corneas. Angiogenic responses were analyzed by immunohistochemistry to quantify blood neovessels (BVs) and lymphatic neovessels (LVs) to 3 weeks after implantation. Areas covered by BV and LV were calculated and expressed as a percentage of the total corneal area (percentage BV and percentage LV). Hemangiogenesis (HA) and lymphangiogenesis (LA) were also assessed after antibody blockade of VEGFR-2 or VEGFR-3
  
  
  RESULTS
  Although high-dose bFGF stimulation induced a more potent angiogenic response, the relative LV (RLV=percentage LV/percentage BV x 100) was nearly identical with high- and low-doses of bFGF. Delayed LA responses induced 3 weeks after implantation of high-dose bFGF resulted in a lymphatic vessel-dominant phenotype. Interestingly, the blockade of VEGFR-2 significantly suppressed BV and LV. However, the blockade of VEGFR-3 inhibited only LV (P=0.0002) without concurrent inhibition of BV (P=0.79), thereby resulting in a blood vessel-dominant phenotype
  
  
  CONCLUSIONS
  An HA-dominant corneal phenotype can be obtained in BALB/c mice 2 weeks after implantation of an 80-ng bFGF micropellet with VEGFR-3 blockade. Alternatively, an LA-dominant corneal phenotype can be obtained 3 weeks after implantation of an 80-ng bFGF micropellet without supplementary modulating agents. These models will be useful in evaluating the differential contribution of BV and LV to a variety of corneal abnormalities, including transplant rejection, wound healing and microbial keratitis.
authors.affiliation: Schepens Eye Research Institute, Boston, Massachusetts 02114, USA.
authors.forename: Eui-Sang
authors.initials: ES
authors.lastname: Chung
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Saban
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Chauhan
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001808:Blood Vessels / Q000502:physiology*; D003315:Cornea / Q000098:blood supply; D016510:Corneal Neovascularization / Q000378:metabolism* / Q000473:pathology; D003319:Corneal Stroma / Q000187:drug effects; D004195:Disease Models, Animal; D004343:Drug Implants; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage; D019084:Fluorescent Antibody Technique, Indirect; D042583:Lymphangiogenesis / Q000502:physiology*; D042601:Lymphatic Vessels / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000037:antagonists & inhibitors
chemical_list: D019138:Antibodies, Blocking; D004343:Drug Implants; D016222:Fibroblast Growth Factor 2; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3