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Afshin Shafiee, John S. Penn, Henry C. Krutzsch, John K. Inman, David D. Roberts, Diane A. Blake; Inhibition of Retinal Angiogenesis by Peptides Derived from Thrombospondin-1. Invest. Ophthalmol. Vis. Sci. 2000;41(8):2378-2388.
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© ARVO (1962-2015); The Authors (2016-present)
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)-β1 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-β1 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
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