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Antonia M. Joussen, Wolf-Dietrich Beecken, Yasufumi Moromizato, Ariane Schwartz, Bernd Kirchhof, Vassiliki Poulaki; Inhibition of Inflammatory Corneal Angiogenesis by TNP-470. Invest. Ophthalmol. Vis. Sci. 2001;42(11):2510-2516.
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purpose. To determine the efficacy of the angiogenic inhibitor TNP-470 on
inflammatory corneal neovascularization. Topical and systemic delivery
of the drug were investigated in a murine model as well as inhibition
of endothelial cell proliferation in vitro and in vivo.
methods. The effect of TNP-470 on VEGF- and bFGF-stimulated bovine capillary
endothelial (BCE) cell proliferation was evaluated in vitro. Corneal
neovascularization was induced in vivo by mechanical debridement of the
corneal and limbal epithelium with 0.15 M NaOH on C57BL6 mice. TNP-470
was administered systemically at 30 mg/kg body weight (BW) every other
day or topically three times daily in a concentration of 5 ng/ml
dissolved in methylcellulose. Vessel length was investigated on day 7.
VEGF protein content in murine corneas was analyzed by ELISA on days 2,
4, and 7 of treatment. A modified bromouridine (BrdU) ELISA was used to
quantify endothelial cell proliferation.
results. TNP-470 exerted a dose-dependent inhibition of bFGF- and VEGF-induced
endothelial cell proliferation in vitro. Both systemic and topical
application of TNP-470 led to a significant reduction of inflammatory
corneal neovascularization (P < 1 ×
10−5). BrdU labeling showed that TNP-470 inhibited
endothelial cell proliferation. VEGF protein levels were reduced by
systemic TNP-470 treatment.
conclusions. These results suggest that TNP-470 reduces inflammatory corneal
angiogenesis by directly inhibiting endothelial cell proliferation.
Topical and systemic treatment with TNP-470 reduces VEGF levels that
are responsible for vessel growth during the neovascularization
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