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Y. Liu, J. Cao, H. Song, D. Dix, D. Hylton, J. S. Rudge, G. D. Yancopoulos, S. J. Wiegand; Inhibition of Corneal Angiogenesis by Topical Administration of VEGF Trap. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1710.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the effect of topical administration of VEGF Trap, a receptor-based fusion protein that binds all isoforms of VEGF-A, on the development of neovascularization following corneal suture injury.
30 C57/BL6 adult male mice were anesthetized with ketamine (120mg/kg) and xylazine (5 mg/kg). Corneal neovascularization (NV) was induced by intrastromal placement of three nylon sutures. VEGF Trap was administered topically three times a day (9:00am, 1:00pm, and 5:00pm), applied as a 4 mcL drop at concentrations of 100, 10, and 1 mg/mL, beginning immediately after injury (day 0). Control animals received vehicle eye drops or drops containing 10 mg/mL of a control protein (human Fc) following the same schedule. Nine days following injury, the corneal vasculature was labeled by intravenous injection of fluorescein conjugated lycopersicon esculentum lectin, and the extent of NV was evaluated post-mortem in corneal flat-mounts. The Scion Image program was used to measure the length of corneal neovessels. Infiltration of leukocytes was evaluated in cross-sections stained with H&E. Serum levels of free (active, unbound) VEGF Trap were determined by ELISA on day 9.
Topical administration of VEGF Trap significantly suppressed corneal NV following the suture placement (98.4% inhibition at a concentration of 100 mg/mL compared with vehicle treated group; 80.6% inhibition at 10 mg/mL compared with hFc treated group; treatment at 1 mg/mL showed only a slight, non-significant reduction in neovascularization). Topical VEGF Trap treatment also markedly reduced inflammation induced by corneal injury. No free VEGF Trap was detected in the serum following 9 days of topical administration (limit of detection, 18.4 ng/mL).
This study demonstrates that topical application of VEGF Trap effectively inhibits of corneal NV and inflammation following suture injury, with no detectable systemic exposure to active drug, even at the highest dose tested.
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