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. Oxygen-induced 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 the most 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.
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. Oxygen-induced 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-mousePECAM-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 the most 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.
Authors: Sara Van de Veire; Ingeborg Stalmans; Femke Heindryckx; Hajimu Oura; Annemilaï Tijeras-Raballand; Thomas Schmidt; Sonja Loges; Imke Albrecht; Bart Jonckx; Stefan Vinckier; Christophe Van Steenkiste; Sònia Tugues; Charlotte Rolny; Maria De Mol; Daniela Dettori; Patricia Hainaud; Lieve Coenegrachts; Jean-Olivier Contreres; Tine Van Bergen; Henar Cuervo; Wei-Hong Xiao; Carole Le Henaff; Ian Buysschaert; Behzad Kharabi Masouleh; Anja Geerts; Tibor Schomber; Philippe Bonnin; Vincent Lambert; Jurgen Haustraete; Serena Zacchigna; Jean-Marie Rakic; Wladimiro Jiménez; Agnes Noël; Mauro Giacca; Isabelle Colle; Jean-Michel Foidart; Gerard Tobelem; Manuel Morales-Ruiz; José Vilar; Patrick Maxwell; Stanley A Vinores; Geert Carmeliet; Mieke Dewerchin; Lena Claesson-Welsh; Evelyne Dupuy; Hans Van Vlierberghe; Gerhard Christofori; Massimiliano Mazzone; Michael Detmar; Désiré Collen; Peter Carmeliet Journal: Cell Date: 2010-04-02 Impact factor: 41.582
Authors: H Ozaki; M S Seo; K Ozaki; H Yamada; E Yamada; N Okamoto; F Hofmann; J M Wood; P A Campochiaro Journal: Am J Pathol Date: 2000-02 Impact factor: 4.307
Authors: Claus Cursiefen; Jingtai Cao; Lu Chen; Ying Liu; Kazuichi Maruyama; David Jackson; Friedrich E Kruse; Stanley J Wiegand; M Reza Dana; J Wayne Streilein Journal: Invest Ophthalmol Vis Sci Date: 2004-08 Impact factor: 4.799
Authors: Danial Roshandel; Medi Eslani; Alireza Baradaran-Rafii; Albert Y Cheung; Khaliq Kurji; Sayena Jabbehdari; Alejandra Maiz; Setareh Jalali; Ali R Djalilian; Edward J Holland Journal: Ocul Surf Date: 2018-06-20 Impact factor: 5.033