Requirement for vascular endothelial growth factor in wound- and inflammation-related corneal neovascularization.
OBJECTIVE
Vascular endothelial growth factor (VEGF) is required for vascular development and for ischemia-related tumor, iris, and retinal neovascularization. The role of VEGF in inflammatory corneal neovascularization is unknown and was investigated in these studies.


METHODS
A rat model was used in which removal of the corneal and limbal epithelium resulted in circumferential neovascularization. Corneal VEGF mRNA levels were quantified with ribonuclease protection assays, and VEGF protein was studied in situ using immunohistochemical analysis. Controlled-release pellets containing anti-VEGF antibodies were implanted into the corneal stroma and were used to determine the requirement for VEGF in corneal neovascularization.


RESULTS
VEGF mRNA and protein were induced to high levels after corneal injury and were temporally and spatially correlated with inflammation and neovascularization. VEGF immunoreactivity was localized primarily to the inflammatory cells invading the wounded cornea. The specific inhibition of VEGF bioactivity with neutralizing antibodies potently suppressed corneal neovascularization.


CONCLUSIONS
These data are the first to demonstrate that VEGF may be required for inflammatory neovascularization of the rat cornea and to identify VEGF as a functional endogenous corneal angiogenic factor.
Amano
S
S
Children's Hospital, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
Rohan
R
R
Kuroki
M
M
Tolentino
M
M
Adamis
A P
AP
D000818:Animals; D003315:Cornea / Q000473:pathology / Q000503:physiopathology; D065306:Corneal Injuries; D016510:Corneal Neovascularization / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D005131:Eye Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007124:Immunoenzyme Techniques; D007634:Keratitis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008222:Lymphokines / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D008297:Male; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014949:Wounds, Nonpenetrating / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D012313:RNA