title: Sustained inhibition of corneal neovascularization by genetic ablation of CCR5.
abstract: OBJECTIVE
  To determine whether genetic ablation of the CC chemokine receptor CCR5 (involved in leukocyte and endothelial chemotaxis) inhibits the development of corneal neovascularization.
  
  
  METHODS
  Wild-type C57BL/6J mice and species-specific counterparts with targeted homozygous disruption of the CCR5 gene underwent chemical and mechanical denudation of corneal and limbal epithelium. Corneas were harvested 2 and 4 weeks after injury. Neovascularization was quantified by CD31 immunostaining. Expression of VEGF protein was quantified by ELISA.
  
  
  RESULTS
  The mean percentages of neovascularized corneal area in control mice and CCR5-deficient mice 2 weeks after denudation were 58.3% and 38.5% (P = 0.05), respectively. At 4 weeks after denudation, the corresponding percentages were 67.6% and 44.0% (P = 0.028). In CCR5-deficient mice, VEGF protein levels were reduced 51.1% at 2 weeks (P = 0.05) after injury and 37.3% at 4 weeks (P = 0.03).
  
  
  CONCLUSIONS
  CCR5-deficient mice showed a persistent 34% to 35% inhibition of corneal neovascularization for up to 4 weeks. This inhibition correlates with reduced expression of VEGF. These data implicate CCR5 as one essential component in the development of corneal neovascularization.
authors.affiliation: Department of Ophthalmology, Medical College of Georgia, Augusta, Georgia, USA.
authors.forename: Balamurali K
authors.initials: BK
authors.lastname: Ambati
authors.forename: Akshay
authors.initials: A
authors.lastname: Anand
authors.forename: Antonia M
authors.initials: AM
authors.lastname: Joussen
authors.forename: William A
authors.initials: WA
authors.lastname: Kuziel
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Adamis
authors.forename: Jayakrishna
authors.initials: J
authors.lastname: Ambati
mesh_terms: D000818:Animals; D002057:Burns, Chemical / Q000209:etiology / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D065306:Corneal Injuries; D016510:Corneal Neovascularization / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016228:Endothelial Growth Factors / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005126:Eye Burns / Q000139:chemically induced / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D017353:Gene Deletion; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D019713:Receptors, CCR5 / Q000235:genetics / Q000502:physiology*; D012972:Sodium Hydroxide; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019713:Receptors, CCR5; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D012972:Sodium Hydroxide