May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Subconjunctival Administration of VEGF Trap Suppresses Corneal Neovascularization
Author Affiliations & Notes
  • J. Cao
    Regeneron Pharm, Inc, Tarrytown, NY
  • H. Song
    Regeneron Pharm, Inc, Tarrytown, NY
  • R. Renard
    Regeneron Pharm, Inc, Tarrytown, NY
  • G.D. Yancopoulos
    Regeneron Pharm, Inc, Tarrytown, NY
  • S.J. Wiegand
    Regeneron Pharm, Inc, Tarrytown, NY
  • Footnotes
    Commercial Relationships  J. Cao, Regeneron Pharmaceuticals, Inc., E; H. Song, Regeneron Pharmaceuticals, Inc., E; R. Renard, Regeneron Pharmaceuticals, Inc., E; G.D. Yancopoulos, Regeneron Pharmaceuticals, Inc., E; S.J. Wiegand, Regeneron Pharmaceuticals, Inc., E.
  • Footnotes
    Support  E
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 2346. doi:
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      J. Cao, H. Song, R. Renard, G.D. Yancopoulos, S.J. Wiegand; Subconjunctival Administration of VEGF Trap Suppresses Corneal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2346.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: To determine the efficacy of subconjunctival delivery of a potent VEGF inhibitor, the VEGF Trap, on the development of neovascularization in animal models of corneal injury. Methods: Corneal neovascularization was induced by intrastromal placement of nylon sutures in male Sprague–Dawley rats, Norway Brown rats or C57BL6 mice, and by chemical injury in mice. The VEGF Trap, a fusion protein comprising portions of the ligand binding domains of VEGF receptors 1 and 2 coupled to human Fc, was administered subconjunctivally (200 µg/eye in rats, 10 µg or 40 µg/eye in mice) , once (at time of injury) or at multiple time points following injury (days 0, 2 and 5). The growth of corneal neovessels was evaluated on days 8 and 12 by slit–lamp microscopy and corneal image analysis. For histological studies, the vasculature was labeled by intravenous injection of a fluorescein conjugated lectin (lycopersicon esculentum) or a solution of hematoxylin and Evans blue, and the extent of neovascularization was evaluated in corneal flat–mounts. Corneal edema was evaluated by slit lamp microscopy. Corneal thickness was measured and polymorphonucleocytes (PMNs) were counted in cross–sections stained with HEMA–3. The Scion Image program was used to measure the area and length of corneal neovessels. Results: Subconjunctival administration of VEGF Trap significantly inhibited corneal neovascularization in all dosing regimens tested, in both suture and chemical injury models. Corneal edema and the infiltration of PMNs into the damaged cornea also were substantially reduced in VEGF Trap treated animals compare to vehicle treated controls (with 28 – 30% decrease in corneal thickness and 40 – 50 % decrease in PMN numbers in cornea 12 days after injury). Conclusions: Subconjunctival administration of VEGF Trap suppresses the development of corneal neovascularization, decreases edema, and markedly reduces the infiltration of leukocytes into the cornea following injury. These results indicate that local delivery of VEGF Trap may have therapeutic applications in the treatment of corneal neovascularization.

Keywords: growth factors/growth factor receptors • neovascularization • inflammation 
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