S. Amano et al., REQUIREMENT FOR VASCULAR ENDOTHELIAL GROWTH-FACTOR IN WOUND-RELATED AND INFLAMMATION-RELATED CORNEAL NEOVASCULARIZATION, Investigative ophthalmology & visual science, 39(1), 1998, pp. 18-22
PURPOSE. Vascular endothelial growth factor (VEGF) is required for vas
cular development and for ischemia-related tumor, iris, and retinal ne
ovascularization. The role of VEGF in inflammatory corneal neovascular
ization is unknown and was investigated in these studies. METHODS. A r
at model was used in which removal of the corneal and limbal epitheliu
m resulted in circumferential neovascularization. Corneal VEGF mRNA le
vels were quantified with ribonuclease protection assays, and VEGF pro
tein was studied in situ using immunohistochemical analysis. Controlle
d-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 mRNB and protein were in
duced to high levels after corneal injury and were temporally and spat
ially correlated with inflammation and neovascularization. VEGF immuno
reactivity was localized primarily to the inflammatory cells invading
the wounded cornea. The specific inhibition of VEGF bioactivity with n
eutralizing 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.