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PEDF-derived peptide inhibits corneal angiogenesis by suppressing VEGF expression.

Abstract
Pigment epithelium-derived factor (PEDF) a glycoprotein that belongs to the superfamily of serine protease inhibitors, has been recently shown to be the most potent inhibitor of angiogenesis in the mammalian eye. However, which active domain of PEDF protein could be involved in its anti-angiogenic properties remains unknown. Therefore, in this study, we examined which PEDF-derived synthetic peptides could inhibit corneal neovascularization induced by chemical cauterization in vivo. Rats treated with topical application of PEDF protein had 31% less corneal neovascularization at day 7 after the injury than phosphate-buffered saline (PBS)-treated rats. P5-2 and P5-3 peptides (residues 388-393 and 394-400 of PEDF protein, respectively) significantly suppressed the corneal neovascularization after chemical cauterization at day 7, and its anti-angiogenic potential was almost equal to that of full-length PEDF protein. Further, full-length PEDF protein and P5-3 peptide significantly decreased 8-hydroxy-2'-deoxyguanosine and vascular endothelial growth factor (VEGF) levels in the corneal. Our present study suggests that PEDF-derived synthetic peptide, P5-3 could inhibit the corneal neovascularization induced by chemical cauterization in rats by suppressing VEGF expression via its anti-oxidative properties.
AuthorsTakanori Matsui, Yuri Nishino, Sayaka Maeda, Sho-ichi Yamagishi
JournalMicrovascular research (Microvasc Res) Vol. 84 Issue 1 Pg. 105-8 (Jul 2012) ISSN: 1095-9319 [Electronic] United States
PMID22386653 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Inc. All rights reserved.
Chemical References
  • Angiogenesis Inhibitors
  • Eye Proteins
  • Nerve Growth Factors
  • Serpins
  • Vascular Endothelial Growth Factor A
  • pigment epithelium-derived factor
  • vascular endothelial growth factor A, rat
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine
Topics
  • 8-Hydroxy-2'-Deoxyguanosine
  • Administration, Topical
  • Angiogenesis Inhibitors (administration & dosage, pharmacology)
  • Animals
  • Cautery
  • Cornea (blood supply, drug effects)
  • Corneal Injuries
  • Corneal Neovascularization (chemically induced, pathology)
  • Deoxyguanosine (analogs & derivatives, metabolism)
  • Disease Models, Animal
  • Eye Proteins (administration & dosage, pharmacology)
  • Male
  • Nerve Growth Factors (administration & dosage, pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Serpins (administration & dosage, pharmacology)
  • Vascular Endothelial Growth Factor A (metabolism)

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