A Peptide Derived from Type 1 Thrombospondin Repeat-Containing Protein WISP-1 Inhibits Corneal and Choroidal Neovascularization

Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, School of Medicine, Baltimore, MD 21231, USA.
Investigative ophthalmology & visual science (Impact Factor: 3.4). 04/2009; 50(8):3840-5. DOI: 10.1167/iovs.08-2607
Source: PubMed


Ocular neovascularization is the primary cause of blindness in a wide range of prevalent ocular diseases including proliferative diabetic retinopathy, exudative age-related macular degeneration, and retinopathy of prematurity, among others. Antiangiogenic therapies are starting to give promising results in these diseases. In the present study the antiangiogenic potential of an 18-mer peptide derived from type 1 thrombospondin repeat-containing protein WISP-1 (wispostatin-1) was analyzed in vitro with human retinal endothelial cell proliferation and migration assays. The peptide was also tested in vivo in the corneal micropocket and the laser-induced choroidal neovascularization (CNV) mouse models.
Human retinal endothelial cells were treated with the WISP-1 peptide and in vitro migration and proliferation assays were performed. Also evaluated was the antiangiogenic effect of this peptide in vivo using the corneal micropocket assay and the laser-induced CNV model.
Wispostatin-1 derived peptide demonstrated antimigratory and antiproliferative activity in vitro. Wispostatin-1 completely abolished bFGF-induced neovascularization in the corneal micropocket assay. The peptide also demonstrated significant inhibition of laser-induced CNV.
An inhibitory effect of Wispostatin-1 on ocular neovascularization was found in vitro and in vivo. The identification of novel and potent endogenous peptide inhibitors provides insight into the pathogenesis of corneal and choroidal neovascularization. The results demonstrate potential for therapeutic application in prevalent ocular disease.

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    • "The glycoprotein thrombospondin-1 suppresses angiogenesis by acting as both an activator of transforming growth factor-β, and a negative regulator of MMP-9 activation, and an activator of apoptotic pathways [52]. Recently a peptide derived from type 1 thrombospondin repeat-containing protein WISP-1 (wispostatin-1) has been shown to have inhibitory effect in vitro as well as in vivo in ocular neovascularization [144]. "
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