VEGF Trap(R1R2) suppresses experimental corneal angiogenesis.
OBJECTIVE
To determine the effect of vascular endothelial growth factor (VEGF) TrapR1R2 on bFGF-induced experimental corneal neovascularization (NV).


METHODS
Control pellets or pellets containing 80 ng bFGF were surgically implanted into wild-type C57BL/6 and VEGF-LacZ mouse corneas. The corneas were photographed, harvested, and the percentage of corneal NV was calculated. The harvested corneas were evaluated for VEGF expression. VEGF-LacZ mice received tail vein injections of an endothelial-specific lectin after pellet implantation to determine the temporal and spatial relationship between VEGF expression and corneal NV. Intraperitoneal injections of VEGF TrapR1R2 or a human IgG Fc domain control protein were administered, and bFGF pellet-induced corneal NV was evaluated.


RESULTS
NV of the corneal stroma began on day 4 and was sustained through day 21 following bFGF pellet implantation. Progression of vascular endothelial cells correlated with increased VEGF-LacZ expression. Western blot analysis showed increased VEGF expression in the corneal NV zone. Following bFGF pellet implantation, the area of corneal NV in untreated controls was 1.05+/-0.12 mm2 and 1.53+/-0.27 mm2 at days 4 and 7, respectively. This was significantly greater than that of mice treated with VEGF Trap (0.24+/-0.11 mm2 and 0.35+/-0.16 mm2 at days 4 and 7, respectively; p<0.05).


CONCLUSIONS
Corneal keratocytes express VEGF after bFGF stimulation and bFGF-induced corneal NV is blocked by intraperitoneal VEGF TrapR1R2 administration. Systemic administration of VEGF TrapR1R2 may have potential therapeutic applications in the management of corneal NV.
Oliveira
Hailton B
HB
The Schepens Eye Research Institute, Harvard Medical School, Boston, MA, USA.
Sakimoto
Tohru
T
Javier
Joel A D
JA
Azar
Dimitri T
DT
Wiegand
Stanley J
SJ
Jain
Sandeep
S
Chang
Jin-Hong
JH
D000818:Animals; D015153:Blotting, Western; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000633:toxicity; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D017978:Receptors, Growth Factor / Q000008:administration & dosage*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D017978:Receptors, Growth Factor; D011993:Recombinant Fusion Proteins; C460365:VEGF Trap R1R2 protein; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D016222:Fibroblast Growth Factor 2