title: Influence of ranibizumab on vascular endothelial growth factor plasma level and endothelial progenitor cell mobilization in age-related macular degeneration patients: safety of intravitreal treatment for vascular homeostasis.
abstract: OBJECTIVE
  Intravitreal ranibizumab, which neutralizes vascular endothelial growth factor (VEGF), nowadays constitutes the first-line treatment in neovascular age-related macular degeneration (AMD). However, its potential systemic effect on vascular homeostasis as the consequence of such therapy has not been extensively investigated.
  
  
  METHODS
  Peripheral blood (PB) samples from 12 patients with newly diagnosed neovascular AMD were analyzed before as well as 1 and 4 weeks after intravitreal treatment with ranibizumab. VEGF plasma levels, the number of circulating endothelial progenitor cells (EPCs), and the intracellular expression of hypoxia-inducible factor (HIF) in PB cells were determined by enzyme-linked immunosorbent assay, flow cytometry, and real-time quantitative reverse transcriptase-polymerase chain reaction assays, respectively.
  
  
  RESULTS
  No significant changes within the analyzed parameters were found in the first or fourth weeks after ranibizumab injection compared with the primary, basic values before treatment. Based on our findings, intravitreal ranibizumab does not induce significant systemic effects or vascular impairment.
  
  
  CONCLUSIONS
  Evaluation of the VEGF plasma level, the PB EPC concentration, and intracellular HIF expression may be supportive indicators of drug safety for ranibizumab.
authors.affiliation: Department of Histology and Embryology, Pomeranian Medical University, Szczecin, Poland. annam@sci.pam.szczecin.p
authors.forename: Anna
authors.initials: A
authors.lastname: Machalińska
authors.forename: Edyta
authors.initials: E
authors.lastname: Paczkowska
authors.forename: Tomasz
authors.initials: T
authors.lastname: Pabin
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Safranow
authors.forename: Danuta
authors.initials: D
authors.lastname: Karczewicz
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Machaliński
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000494:pharmacology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D000069579:Ranibizumab; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D051792:Basic Helix-Loop-Helix Proteins; D012333:RNA, Messenger; D000069579:Ranibizumab; D042461:Vascular Endothelial Growth Factor A