Inhibition of retinal angiogenesis by peptides derived from thrombospondin-1.

Shafiee A, Penn JS, Krutzsch HC, Inman JK, Roberts DD, Blake DA
Invest Ophthalmol Vis Sci. 2000 41 (8): 2378-88

PMID: 10892887

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.

MeSH Terms (19)

Amino Acid Sequence Animals Animals, Newborn Cattle Disease Models, Animal Dose-Response Relationship, Drug Female Humans Infant, Newborn Male Molecular Sequence Data Peptide Fragments Rats Rats, Sprague-Dawley Retinal Neovascularization Retinal Vessels Retinopathy of Prematurity Thrombospondin 1 Time Factors

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