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David Hui-Kang Ma, Ray Jui-Fang Tsai, Wing-Keung Chu, Cheng-Heng Kao, Jan-Kan Chen; Inhibition of Vascular Endothelial Cell Morphogenesis in Cultures by Limbal Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 1999;40(8):1822-1828.
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purpose. To study the in vitro angiogenic activity of human conjunctival and limbal
epithelial cells and conjunctival, limbal, and corneal fibroblasts in a
three-cell-type coculture model.
methods. Human umbilical vein endothelial cells (EC) were cocultured with
epithelial cells, fibroblasts, or epithelial cells and fibroblasts to
test their effect on EC morphogenesis. Neutralizing antibodies to some
known angiogenic factors were added to the culture to see whether the
EC morphogenesis may be blocked by a particular antibody.
results. Conjunctival and limbal epithelial cells exhibited very little or no
stimulatory effect on EC tube formation when examined in an
EC–epithelial cell coculture system. In contrast, conjunctival,
limbal, and corneal fibroblasts all promoted EC morphogenesis when
examined under the same culture conditions. Fibroblast-induced EC
morphogenesis was inhibited by addition of anti-vascular endothelial
growth factor (VEGF) and/or anti-basic fibroblast growth factor (bFGF)
antibodies to the culture medium. In the three-cell-type coculture
system consisting of ECs, fibroblasts, and epithelial cells, limbal
epithelial cells (but not conjunctival epithelial cells) exhibited a
strong inhibitory effect on fibroblast-induced EC tube formation.
conclusions. The proangiogenic activity of ocular surface fibroblasts is probably
mediated through a paracrine mechanism by VEGF and bFGF. Limbal
epithelial cells, but not conjunctival epithelial cells, inhibit
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