Bm. Kenyon et al., EFFECTS OF THALIDOMIDE AND RELATED METABOLITES IN A MOUSE CORNEAL MODEL OF NEOVASCULARIZATION, Experimental Eye Research, 64(6), 1997, pp. 971-978
Thalidomide, when administered orally, is an inhibitor of angiogenesis
in the basic fibroblast growth factor (bFGF)-induced rabbit cornea mi
cropocket assay. We now show in the mouse that thalidomide given intra
peritoneally but not orally significantly inhibits bFGF-induced and va
scular endothelial growth factor (VEGF)-induced corneal neovasculariza
tion, We further demonstrate that this inhibition is independent from
thalidomide's ability to suppress tumor necrosis factor-alpha (TNF-alp
ha) production. Experiments examining thalidomide's enantiomers reveal
that the S(-)-enantiomer has the strongest antiangiogenic activity in
VEGF-induced and bFGF-induced corneal neovascularization. Structure a
ctivity studies suggest that thalidomide's anti-angiogenic activity is
related to the open ring metabolites resulting from hydrolysis. Toget
her these data support a correlation between thalidomide's antiangioge
nic and teratogenic activities. (C) 1997 Academic Press Limited.