title: Endothelial progenitor cells and response to ranibizumab in age-related macular degeneration.
abstract: BACKGROUND
  Choroidal neovascularization (CNV) is the main cause of vision loss in age-related macular degeneration (AMD). In experimental CNV, endothelial progenitor cells (EPCs) contribute to the formation of new vessels. The aim of this study was to investigate whether the behavior of EPCs in patients with AMD supports a role for EPCs in human CNV.
  
  
  METHODS
  The number of circulating EPCs that are considered pure endothelial precursors and EPCs with monocytic characteristics, and the plasma levels of regulatory cytokines were evaluated in 23 patients with AMD with active CNV and 20 matched controls. In the patients, this profile was re-evaluated after ranibizumab.
  
  
  RESULTS
  When compared with controls, the patients with AMD showed a lower number of both EPC types (P = 0.03) and higher plasma levels (P = 0.03) of stromal cell-derived factor 1. Three monthly injections of ranibizumab returned to control levels the number of circulating EPCs considered pure endothelial precursors and of stromal cell-derived factor 1, but not of monocytic EPCs.
  
  
  CONCLUSIONS
  The observations indicate responsiveness of circulating EPCs to the CNV process in AMD. They suggest the hypothesis that increased stromal cell-derived factor 1 production at the CNV site (reflected in higher plasma levels) recruits EPCs from the circulation, and that antivascular endothelial growth factor therapy selectively decreases the recruitment of cells to be incorporated into new vessels.
authors.affiliation: *Department of Ophthalmology, †Diabetes Complications Unit, and ‡Flow Cytometry Resource Laboratory, San Raffaele Scientific Institute, Milan, Italy; and §Department of Ophthalmology, Schepens Eye Research Institute Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Scotti
authors.forename: Anna
authors.initials: A
authors.lastname: Maestroni
authors.forename: Alessio
authors.initials: A
authors.lastname: Palini
authors.forename: Ugo
authors.initials: U
authors.lastname: Introini
authors.forename: Marco
authors.initials: M
authors.lastname: Setaccioli
authors.forename: Mara
authors.initials: M
authors.lastname: Lorenzi
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Zerbini
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018952:Antigens, CD34 / Q000097:blood; D054377:Chemokine CXCL12 / Q000097:blood; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000503:physiopathology; D016207:Cytokines / Q000097:blood; D066026:Endothelial Progenitor Cells / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D058449:Intravitreal Injections; D017493:Leukocyte Common Antigens / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008268:Macular Degeneration / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D000069579:Ranibizumab; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D018952:Antigens, CD34; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; D000069579:Ranibizumab