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

J Ocul Pharmacol Ther. 2011 Oct;27(5):471-5. doi: 10.1089/jop.2011.0091. Epub 2011 Aug 10.

Abstract

Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / pharmacology*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Gene Expression Regulation / drug effects
  • Humans
  • Macular Degeneration / drug therapy*
  • Macular Degeneration / physiopathology
  • Male
  • RNA, Messenger / metabolism
  • Ranibizumab
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Basic Helix-Loop-Helix Transcription Factors
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Ranibizumab