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


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 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.


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.
Cano
Marisol del Valle
Mdel V
Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, School of Medicine, Baltimore, MD 21231, USA.
Karagiannis
Emmanouil D
ED
Soliman
Mohamed
M
Bakir
Belal
B
Zhuang
Wenjuan
W
Popel
Aleksander S
AS
Gehlbach
Peter L
PL
D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D055511:CCN Intercellular Signaling Proteins; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007267:Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000737:chemistry / Q000627:therapeutic use*; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins; D012171:Retinal Vessels / Q000166:cytology; D014822:Vitreous Body
D020533:Angiogenesis Inhibitors; D055511:CCN Intercellular Signaling Proteins; C492067:CCN4 protein, mouse; D015513:Oncogene Proteins; D010455:Peptides; D011518:Proto-Oncogene Proteins