Graefe's Archive for Clinical and Experimental Ophthalmology

, Volume 245, Issue 12, pp 1837–1842

Comparative antiproliferative and cytotoxic profile of bevacizumab (Avastin), pegaptanib (Macugen) and ranibizumab (Lucentis) on different ocular cells

  • Martin S. Spitzer
  • Efdal Yoeruek
  • Ana Sierra
  • Barbara Wallenfels-Thilo
  • Ulrich Schraermeyer
  • Bernhard Spitzer
  • Karl U. Bartz-Schmidt
  • Peter Szurman
Retinal disorders

DOI: 10.1007/s00417-007-0568-7

Cite this article as:
Spitzer, M.S., Yoeruek, E., Sierra, A. et al. Graefes Arch Clin Exp Ophthalmol (2007) 245: 1837. doi:10.1007/s00417-007-0568-7

Abstract

Aim

To compare the antiproliferative and cytotoxic properties of bevacizumab (Avastin), pegaptanib (Macugen) and ranibizumab (Lucentis) on human retinal pigment epithelium (ARPE19) cells, rat retinal ganglion cells (RGC5) and pig choroidal endothelial cells (CEC).

Methods

Monolayer cultures of ARPE19, RGC5 and CEC were used. Bevacizumab (0.1–0.3 mg/ml), pegaptanib (0.025–0.08 mg/ml) or ranibizumab (0.04–0.125 mg/ml) diluted in culture medium were added to the cells. Expression of VEGF-receptors (VEGFR1 and VEGFR2) and von Willebrand factor (a marker for endothelial cells) were analysed by immunohistochemistry. CEC cells were stimulated with VEGF. Cellular proliferative activity was monitored by BrdU-incorporation into cellular DNA. For cytotoxicity assays cells were grown to confluence and then cultured in a serum-depleted medium to ensure a static milieu. MTT-test was performed after one day.

Results

CEC and ARPE19 cells stained positively for VEGFR1 and VEGFR2. More than 95% of the CEC cells were positive for von Willebrand factor. Ranibizumab reduced CEC cell proliferation by 44.1%, bevacizumab by 38.2% and pegaptanib by 35.1% when the drugs were used at their established clinical doses. The differences, however, between the three drugs in respect to cell growth inhibition were not statistically significant. Only a mild antiproliferative effect of bevacizumab or pegaptanib on ARPE19 cells could be observed. Ranibizumab did not alter ARPE19 cell proliferation. No cytotoxicity on RGC5, CEC and ARPE19 cells could be seen.

Conclusions

Bevacizumab, pegaptanib and ranibizumab significantly suppress choroidal endothelial cell proliferation. However, when used at the currently established doses none of the drugs was superior over the others in respect to endothelial cell growth inhibition. The biocompatibility of all three drugs — including the off-label bevacizumab — seems to be excellent when used at the currently recommended intravitreal dose.

Keywords

Bevacizumab (Avastin)Pegaptanib (Macugen)Ranibizumab (Lucentis)Ocular cellsAntiproliferative

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Martin S. Spitzer
    • 1
  • Efdal Yoeruek
    • 1
  • Ana Sierra
    • 1
  • Barbara Wallenfels-Thilo
    • 1
  • Ulrich Schraermeyer
    • 1
  • Bernhard Spitzer
    • 2
  • Karl U. Bartz-Schmidt
    • 1
  • Peter Szurman
    • 1
  1. 1.University Eye Clinic Tuebingen, Department IEberhard-Karls University TuebingenTuebingenGermany
  2. 2.Department of Experimental PsychologyUniversity of RegensburgRegensburgGermany