December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
VEGF-dependent Conjunctivalization of the Corneal Surface
Author Affiliations & Notes
  • PJ Esser
    Dept of vitreoretinal surgery University of Cologne Cologne Germany
  • AM Joussen
    Dept of vitreoretinal surgery University of Cologne Cologne Germany
  • V Poulaki
    Massachussetts Eye and Ear InfirmaryHarvard Medical School Boston MA
  • SU Stechschulte
    Massachussetts Eye and Ear InfirmaryHarvard Medical School Boston MA
  • B Kirchhof
    Dept of vitreoretinal surgery University of Cologne Cologne Germany
  • D Dart
    Schepens Eye Institute Harvard Medical School Boston MA
  • GH Fong
    Mount Sinai Hospital Toronto ON Canada
  • SJ Wiegand
    Regeneron Pharmaceuticals Inc Tarrytown NY
  • GD Yancopoulos
    Regeneron Pharmaceuticals Inc Tarrytown NY
  • AP Adamis
    Massachussetts Eye and Ear Infirmary Harvard Medical School Boston MA
  • Footnotes
    Commercial Relationships   P.J. Esser, None; A.M. Joussen, None; V. Poulaki, None; S.U. Stechschulte, None; B. Kirchhof, None; D. Dart, None; G.H. Fong, None; S.J. Wiegand, Regeneron Pharmaceuticals Inc. E; G.D. Yancopoulos, Regeneron Pharmaceuticals Inc. E; A.P. Adamis, Regeneron Pharmaceuticals Inc. P. Grant Identification: DFG Jo 324/4-1, JDF (AMJ), RSF, NIH (APA)
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 3165. doi:
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    • Get Citation

      PJ Esser, AM Joussen, V Poulaki, SU Stechschulte, B Kirchhof, D Dart, GH Fong, SJ Wiegand, GD Yancopoulos, AP Adamis; VEGF-dependent Conjunctivalization of the Corneal Surface . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3165.

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

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Abstract

Abstract: : Purpose:To investigate the mechanisms governing corneal neovascularization and conjunctivalization in a model of limbal insufficiency. Methods:In a murine model of limbal insufficiency and inflammatory angiogenesis, the spatial and time-dependent relationship between corneal neovascularization and goblet cell appearance was analyzed in corneal flat mounts and paraffin sections. Flt-1 expression was analyzed via Western blot, northern blot, immunohistochemistry, and in transgenic mice overexpressing lacZ targeted to the flt-1 locus through homologous recombination. VEGF inhibition, via systemic adenoviral soluble Flt-1 expression, was studied for its effects on corneal neovascularization and conjunctivalization. Results:Corneal neovascularization is temporally and spatially correlated with corneal goblet cell appearance. The expression of the VEGF receptor Flt-1 is markedly increased in the epithelium and invading leukocytes of the cornea. With the onset of corneal neovascularization, Flt-1 is also localized to vascular endothelial cells, as well as goblet cells in the epithelium. Isolated human and rat goblet cells also express Flt-1 mRNA and protein. The inhibition of VEGF activity via soluble Flt-1 reduced corneal vascularization (P< 0.05) and goblet cell invasion (P< 0.02). Conclusion:These results indicate that corneal conjunctivalization, including both goblet cell appearance and neovascularization, is regulated via VEGF. Goblet cells bear the Flt-1 receptor and appear in response to increased VEGF levels following limbal stem cell debridement. Thus anti-VEGF therapy may help restrict the development of pathological sequelae following limbal injury.

Keywords: 365 conjunctiva • 483 neovascularization • 423 growth factors/growth factor receptors 
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