Effects of bevacizumab on retinal function in isolated vertebrate retina.
BACKGROUND
Bevacizumab (Avastin) is a recombinant protein that targets vascular endothelial growth factor (VEGF). In vitro, bevacizumab inhibits VEGF induced cell proliferation and tissue factor production. Abnormal angiogenesis involving VEGF is a central event during the development of choroidal neovascularisation (CNV). The present study was designed to evaluate the short term toxic effects of bevacizumab on retinal function for a therapeutic intraocular application.


METHODS
Isolated bovine retinas were perfused with an oxygen pre-incubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using silver/silver chloride electrodes. Bevacizumab was added in different concentrations to the nutrient solution for 45 minutes. Thereafter the retina was reperfused for 60 minutes with normal nutrient solution. The percentage of a-wave and b-wave reduction during the application of bevacizumab was calculated and compared to control recordings.


RESULTS
During the application of three different concentrations of bevacizumab (0.08 mg/ml, 0.25 mg/ml, 0.8 mg/ml) no significant reduction of the a-wave and b-wave amplitude was observed. During the washout, the ERG amplitudes were unchanged.


CONCLUSIONS
The present study suggests that an intraocular application of 0.25 mg/ml bevacizumab for the treatment of CNV is reasonable. No significant short term effects of bevacizumab on retinal function were detected, but long term effects cannot be excluded.
Lüke
M
M
University Eye Hospital, Centre for Ophthalmology, Eberhard-KarlsUniversity of Tuebingen, Schleichstrasse 12-16, D-72076, Tuebingen, Germany. matthias.lueke@med.uni-tuebingen.de
Warga
M
M
Ziemssen
F
F
Gelisken
F
F
Grisanti
S
S
Schneider
T
T
Lüke
C
C
Partsch
M
M
Bartz-Schmidt
K U
KU
Szurman
P
P
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography / Q000187:drug effects; D012160:Retina / Q000187:drug effects* / Q000502:physiology; D046509:Tissue Culture Techniques
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab