title: A PEDF-derived peptide inhibits retinal neovascularization and blocks mobilization of bone marrow-derived endothelial progenitor cells.
abstract: Proliferative diabetic retinopathy is characterized by pathological retinal neovascularization, mediated by both angiogenesis (involving mature endothelial cells) and vasculogenesis (involving bone marrow-derived circulating endothelial progenitor cells (EPCs)). Pigment epithelium-derived factor (PEDF) contains an N-terminal 34-amino acid peptide (PEDF-34) that has antiangiogenic properties. Herein, we present a novel finding that PEDF-34 also possesses antivasculogenic activity. In the oxygen-induced retinopathy (OIR) model using transgenic mice that have Tie2 promoter-driven GFP expression, we quantified Tie2GFP(+) cells in bone marrow and peripheral blood by fluorescence-activated cell sorting (FACS). OIR significantly increased the number of circulating Tie2-GFP(+) at P16, correlating with the peak progression of neovascularization. Daily intraperitoneal injections of PEDF-34 into OIR mice decreased the number of Tie2-GFP(+) cells in the circulation at P16 by 65% but did not affect the number of Tie2-GFP(+) cells in the bone marrow. These studies suggest that PEDF-34 attenuates EPC mobilization from the bone marrow into the blood circulation during retinal neovascularization.
authors.affiliation: Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma, OK 73104, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Longeras
authors.forename: Krysten
authors.initials: K
authors.lastname: Farjo
authors.forename: Michael
authors.initials: M
authors.lastname: Ihnat
authors.forename: Jian-Xing
authors.initials: JX
authors.lastname: Ma
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000166:cytology / Q000187:drug effects; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005136:Eye Proteins / Q000378:metabolism / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D010100:Oxygen / Q000009:adverse effects; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism; D015861:Retinal Neovascularization / Q000503:physiopathology*; D015843:Serpins / Q000378:metabolism / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D049452:Green Fluorescent Proteins; D009414:Nerve Growth Factors; D010100:Oxygen; D010455:Peptides; D042787:Receptor, TIE-2; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor