Sustained inhibition of corneal neovascularization by genetic ablation of CCR5.
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.
Ambati
Balamurali K
BK
Department of Ophthalmology, Medical College of Georgia, Augusta, Georgia, USA.
Anand
Akshay
A
Joussen
Antonia M
AM
Kuziel
William A
WA
Adamis
Anthony P
AP
Ambati
Jayakrishna
J
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
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