Effect of thalidomide and structurally related compounds on corneal angiogenesis is comparable to their teratological potency

Citation
Am. Joussen et al., Effect of thalidomide and structurally related compounds on corneal angiogenesis is comparable to their teratological potency, GR ARCH CL, 237(12), 1999, pp. 952-961
Citations number
33
Categorie Soggetti
Optalmology
Journal title
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
ISSN journal
0721832X → ACNP
Volume
237
Issue
12
Year of publication
1999
Pages
952 - 961
Database
ISI
SICI code
0721-832X(199912)237:12<952:EOTASR>2.0.ZU;2-T
Abstract
Neovascular diseases are the leading causes of blindness in humans. Althoug h several promissing compounds have been isolated, pharmacological treatmen t remains difficult. Thalidomide has inhibitory effects on angiogenesis in the corneal micropocket assay. However, the results vary considerably depen ding on the administration route and ani mal model. The aim of this study, therefore, was to investigate thalidomide and two of its derivatives, supid imide and EM12, in the rabbit corneal micropocket assay. Using both basic f ibroblast growth factor and vascular endothelial growth factor for initiati on of the neovascular response, we were able to show a significant inhibiti on of neovascularisation with all three substances. EM12, the most teratoge nic derivative analysed, was demonstrated to be the most potent inhibitor o f angiogenesis in this model. Thalidomide and supidimide did not show syste mic side effects in the applied dosage. An equal dosage of EM12, however, r esulted in significant weight loss of the animals, but did not increase ang iogenic activity compared with lower doses. Together with earlier findings, these data support a strong correlation between the antiangiogenic potenti al and the teratogenic activity of thalidomide and structurally related com pounds.