Parstatin suppresses ocular neovascularization and inflammation

Hu Huang, Panagiotis Vasilakis, Xiufeng Zhong, Ji Kui Shen, Katerina Geronatsiou, Helen Papadaki, Michael E. Maragoudakis, Sotirios P. Gartaganis, Stanley A. Vinores, Nikos E. Tsopanoglou

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE. Parstatin is a 41-mer peptide formed by proteolytic cleavage on activation of the PAR1 receptor. The authors recently showed that parstatin is a potent inhibitor of angiogenesis. The purpose of the present study was to evaluate the therapeutic effect of parstatin on ocular neovascularization. METHODS. Choroidal neovascularization was generated in mice using laser-induced rupture of Bruch's membrane and was assessed after 14 days after perfusion of FITC-dextran. Oxygeninduced retinal neovascularization was established in neonatal mice by exposing them to 75% O 2 at postnatal day (P)7 for 5 days and then placing them in room air for 5 days. Evaluation was performed on P17 after staining with anti-mouse PECAM-1. The effect of parstatin was tested after intravitreal administration. The effects of subconjunctival-injected parstatin on corneal neovascularization and inflammation in rats were assessed 7 days after chemical burn-induced corneal neovascularization. Retinal leukostasis in mice was assessed after perfusion with FITC-conjugated concanavalin A. RESULTS. Parstatin potently inhibited choroidal neovascularization with an IC 50 of approximately 3 μg and a maximum inhibition of 59% at 10 μg. Parstatin suppressed retinal neovascularization with maximum inhibition of 60% at 3 μg. Ten-microgram and 30-μg doses appeared to be toxic to the neonatal retina. Subconjunctival parstatin inhibited corneal neovascularization, with 200 μg themost effective dose (59% inhibition). In addition, parstatin significantly inhibited corneal inflammation and VEGF-induced retinal leukostasis. In all models tested, scrambled parstatin was without any significant effect. CONCLUSIONS. Parstatin is a potent antiangiogenic agent of ocular neovascularization and may have clinical potential in the treatment of angiogenesis-related ocular disorders.

Original languageEnglish (US)
Pages (from-to)5825-5832
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume51
Issue number11
DOIs
StatePublished - Nov 2010

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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