Inhibition of retinal angiogenesis by peptides derived from thrombospondin-1.
Invest Ophthalmol Vis Sci
; 41(8): 2378-88, 2000 Jul.
Article
em En
| MEDLINE
| ID: mdl-10892887
ABSTRACT
PURPOSE:
Thrombospondin (TSP)1 is a tumor suppressor with activity that is associated with its ability to inhibit neovascularization. Previous studies have mapped this antiangiogenic activity to the type 1 repeats and the amino-terminal portion of the molecule within the procollagen-like domain. The present study was performed to investigate the ability of TSP-1 and peptides derived from the type 1 repeats to inhibit retinal angiogenesis.METHODS:
TSP-1 and peptides with tryptophan-rich, heparin-binding sequences and transforming growth factor (TGF)-beta1 activation sequences were evaluated in two models of retinal angiogenesis a retinal explant assay and a rat model of retinopathy of prematurity (ROP).RESULTS:
Platelet-derived TSP-1 inhibited angiogenesis in both experimental models. Peptides from the native TSP-1 sequence, which contained both the tryptophan-rich repeat and the TGF-beta1 activation sequence, were the most potent inhibitors of endothelial cell outgrowth in the retinal explant assay. In contrast, a peptide containing only the tryptophan-rich, heparin-binding sequence was most active in inhibiting neovascular disease in the rat ROP model.CONCLUSIONS:
These results indicate that the type 1 repeats of TSP-1 contain two subdomains that may independently influence the process of neovascularization, and that peptides derived from these type 1 repeats may be promising pharmacologic agents for treatment of retinal angiogenesis.
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Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Neovascularização Retiniana
/
Trombospondina 1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
/
Male
/
Newborn
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article