gms | German Medical Science

102. Jahrestagung der DOG

Deutsche Ophthalmologische Gesellschaft e. V.

23. bis 26.09.2004, Berlin

VEGF-dependent conjunctivalization of the corneal surface

Meeting Abstract

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Evidenzbasierte Medizin - Anspruch und Wirklichkeit. 102. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft. Berlin, 23.-26.09.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04dogSA.14.03

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Published: September 22, 2004

© 2004 Joussen.
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To investigate the mechanisms governing corneal neovascularization and goblet cell appearance in a murine model of limbal insufficiency.


The spatial and time-dependent relationship between corneal neovascularization and goblet cell density was analyzed in corneal flat mounts. Immunohistochemical detection of the vascular endothelial growth factor (VEGF) receptor Flt-1 (VEGFR1) was performed in paraffin sections. A transgenic mouse expressing the reporter gene lacZ targeted to the flt-1 locus through homologous recombination was used to analyze corneal Flt-1 expression. The presence of soluble and membranous goblet cell Flt-1 mRNA and protein content was assessed with Northern and Western blotting, respectively. Finally, systemic adenoviral expression of a soluble Flt-1/Fc construct was used to study the effect of VEGF bioactivity inhibition on goblet cell appearance and neovascularization.


Corneal neovascularization preceded the appearance of corneal goblet cells, although both processes overlapped temporally. The VEGF receptor Flt-1 was abundant in the conjunctiva-like epithelium covering the cornea, goblet cells, invading leukocytes and the neovasculature. A similar expression pattern was observed in transgenic mice expressing the lacZ gene downstream from the Flt-1 promotor. Isolated human and rat goblet cells in culture expressed Flt-1 mRNA and protein, as did human conjunctiva. The systemic inhibition of VEGF bioactivity potently suppressed both corneal neovascularization (8.3 ±8.1 vs. 41.1±15.3 % corneal area; P< 0.001) and corneal goblet cell density (1.6±2.5 vs. 12.2±2.4 % corneal area; P< 0.001).


Two important features of corneal conjunctivalization, goblet cell appearance and neovascularization, are regulated via VEGF. Both processes are likely mediated, in part, via the Flt-1 receptor. Taken together, these data indicate that anti-VEGF therapies may limit the vision threatening consequences that follow limbal injury.