A peptide derived from type 1 thrombospondin repeat-containing protein WISP-1 inhibits corneal and choroidal neovascularization

Marisol del Valle Cano, Emmanouil D. Karagiannis, Mohamed Soliman, Belal Bakir, Wenjuan Zhuang, Aleksander S. Popel, Peter L. Gehlbach

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

PURPOSE. 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 antiangio-genic potential of an 18-mer peptide derived from type 1 thrombospondin repeat-containing protein WISP-1 (wisposta-tin-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 cho-roidal neovascularization (CNV) mouse models. METHODS. 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. Results. Wispostatin-1 derived peptide demonstrated antimi-gratory 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. CONCLUSIONS. 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.

Original languageEnglish (US)
Pages (from-to)3840-3845
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume50
Issue number8
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

Corneal Neovascularization
Thrombospondin 1
Choroidal Neovascularization
Tin
Peptides
Proteins
Lasers
Eye Diseases
Endothelial Cells
Cell Migration Assays
Retinopathy of Prematurity
Macular Degeneration
Diabetic Retinopathy
Blindness
Cell Proliferation
In Vitro Techniques
Therapeutics

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

A peptide derived from type 1 thrombospondin repeat-containing protein WISP-1 inhibits corneal and choroidal neovascularization. / Cano, Marisol del Valle; Karagiannis, Emmanouil D.; Soliman, Mohamed; Bakir, Belal; Zhuang, Wenjuan; Popel, Aleksander S.; Gehlbach, Peter L.

In: Investigative Ophthalmology and Visual Science, Vol. 50, No. 8, 2009, p. 3840-3845.

Research output: Contribution to journalArticle

Cano, Marisol del Valle ; Karagiannis, Emmanouil D. ; Soliman, Mohamed ; Bakir, Belal ; Zhuang, Wenjuan ; Popel, Aleksander S. ; Gehlbach, Peter L. / A peptide derived from type 1 thrombospondin repeat-containing protein WISP-1 inhibits corneal and choroidal neovascularization. In: Investigative Ophthalmology and Visual Science. 2009 ; Vol. 50, No. 8. pp. 3840-3845.
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AU - Soliman, Mohamed

AU - Bakir, Belal

AU - Zhuang, Wenjuan

AU - Popel, Aleksander S.

AU - Gehlbach, Peter L.

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N2 - PURPOSE. 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 antiangio-genic potential of an 18-mer peptide derived from type 1 thrombospondin repeat-containing protein WISP-1 (wisposta-tin-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 cho-roidal neovascularization (CNV) mouse models. METHODS. 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. Results. Wispostatin-1 derived peptide demonstrated antimi-gratory 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. CONCLUSIONS. 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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