May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Long-lasting Inhibition of Corneal Neovascularization following Systemic Administration of the VEGF Trap
Author Affiliations & Notes
  • S.J. Wiegand
    Regeneron Pharmaceuticals Inc, Tarrytown, NY, United States
  • J. Cao
    Regeneron Pharmaceuticals Inc, Tarrytown, NY, United States
  • R. Renard
    Regeneron Pharmaceuticals Inc, Tarrytown, NY, United States
  • J.S. Rudge
    Regeneron Pharmaceuticals Inc, Tarrytown, NY, United States
  • G.D. Yancopoulos
    Regeneron Pharmaceuticals Inc, Tarrytown, NY, United States
  • Footnotes
    Commercial Relationships  S.J. Wiegand, Regeneron Pharmaceuticals, Inc. E; J. Cao, Regeneron Pharmaceuticals, Inc. E; R. Renard, Regeneron Pharmaceuticals, Inc. E; J.S. Rudge, Regeneron Pharmaceuticals, Inc. E; G.D. Yancopoulos, Regeneron Pharmaceuticals, Inc. E.
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 829. doi:
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      S.J. Wiegand, J. Cao, R. Renard, J.S. Rudge, G.D. Yancopoulos; Long-lasting Inhibition of Corneal Neovascularization following Systemic Administration of the VEGF Trap . Invest. Ophthalmol. Vis. Sci. 2003;44(13):829.

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

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Abstract

Abstract: : Purpose: To determine whether inhibition of vascular endothelial growth factor (VEGF) during the period of corneal re-epithelialization can produce a long-lasting inhibition of corneal neovascularization following injury. Methods: Corneal neovascularization was induced by application of NaOH and mechanical debridement of the corneal epithelium in adult, male C57BL/6 mice. The VEGF Trap (a fusion protein comprising the ligand binding domains of VEGF receptors 1 and 2 and human Fc) or a control protein (human Fc) were administered subcutaneously (12.5 mg/kg) on days 0 (the day of injury), 7 and 14 when re-epithelialization of the cornea was complete. The animals were euthanized on days 28 or 42 (14 or 28 days following the last injection of VEGF Trap) and corneas taken for histological evaluation. The vasculature was labeled with fluorescein conjugated lectin (lycopersicon esculentum), and neovascularization was evaluated in corneal flat-mount, as well as in cross sections using PECAM immunohistochemistry. The histological appearance of the re-epithelialized cornea was evaluated in cross-sections stained with hematoxylin and eosin. Results: Treatment with VEGF Trap inhibited corneal neovascularization, not only during the period of active treatment, but also 2 and 4 weeks following treatment cessation. In eyes evaluated on day 28 (14 days after the last injection of VEGF Trap), the neovascular response to injury remained completely suppressed and conjuntivalization of the cornea also was effectively inhibited as evidenced by a more normal appearing morphology of the re-epithelialized cornea and a substantial reduction in goblet cell number (~30% relative to controls). Corneal inflammation and edema also were reduced substantially. Evaluation of flat-mounted corneas taken at day 42 showed that neovascularization was still largely suppressed, though limited, focal sprouting of vessels at the corneal margin was observed in some cases. Conclusions: When administered at the time of injury, VEGF Trap potently inhibits the development of corneal neovascularization, inflammation and edema and also inhibits conjunctivalization of the cornea. These effects persist for weeks following cessation of treatment, suggesting that acute inhibition of VEGF following corneal injury may have long-term benefits.

Keywords: inflammation • neovascularization • wound healing 
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