1Joussen A. M., 2Poulaki V., 1Kirchhof B., 2Adamis A. P.

1Dept. of Vitreoretinal Surgery, University of Cologne, Germany, 2Massachussetts Eye and Ear Infirmary, Harvard Medical School; Boston MA, USA

Purpose: To investigate the regulatory mechanisms governing the corneal neovascularization and transdifferentiation in limbal insufficiency and inflammatory angiogenesis.
Methods: In a murine model of limbal insufficiency and inflammatory angiogenesis, the spatial and time-dependent relationship between neovascularization and goblet cell migration on the corneal surface was analyzed in flat mount and in paraffin sections. Immunohistochemical detection of Flt-1 expression was performed in paraffin sections. Finally, the effect of VEGF inhibition by systemic application of soluble Flt-1 via an adenoviral approach was investigated in respect to transdifferentiation and stromal vascularization.
Results: The extent of corneal neovascularization correlates with the extent of goblet cell migration into the epithelium. Although no direct spatial correlation was found, goblet cell invasion seemed to follow corneal neovascularization in a quantitative and time dependent manner. After experimental induction of limbal insufficiency, the expression of the VEGF receptor Flt-1 was markedly increased in the epithelium and in invading leukocytes. Upon beginning of the stromal neovascularization, Flt-1 was also found in vascular endothelial cells as well as in goblet cells in the epithelium. The inhibition of VEGF by soluble Flt-1 reduced corneal vascularization (P< 0.05) and goblet cell invasion (P< 0.02).
Conclusions: These results demonstrate that in limbal insufficiency both epithelial transdifferentiation as well as stromal neovascularization are regulated via VEGF. Thus anti-VEGF therapy may help restrict the development of pathological sequelae following limbal injury. DFG Jo 324/2-1

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