Effects of the protein tyrosine kinase inhibitor genistein and taurine on retinal function in isolated superfused retina.
BACKGROUND
Genistein has the potential to act as an intraocular antiangiogenic agent. Its therapeutical use, however, is limited by toxic side effects on the retina. This study was designed to evaluate the simultaneous use of taurine as a neuroprotective drug.


METHODS
Bovine retinas were isolated and perfused with an oxygen-preincubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal electrical potential using Ag/AgCl electrodes. At stable ERG amplitudes, genistein at concentrations of 11, 37, and 150 microM was added to the nutrient solution for 45 min, in the absence or presence of taurine (3 mM). Thereafter, the retina was reperfused with the nutrient solution for another 100 min. The percentage of b-wave reduction during genistein and genistein/taurine application was calculated.


RESULTS
The b-wave amplitude was reduced by a smaller amount during the application of genistein (11 and 37 microM) in the presence of taurine compared with genistein alone. For both, genistein/taurine and genistein alone the b-wave recovered completely during the wash-out of the drugs. However, during the application of the highest tested concentration of genistein (150 microM), taurine did not protect completely, leading to an irreversible b-wave reduction.


CONCLUSIONS
The adjuvant use of taurine reduces the genistein-induced retinal toxicity to a certain degree. However, the protective effect of taurine is limited and there is only a narrow therapeutic index for a combined intravitreal administration of genistein in coapplication with taurine to inhibit pathological ocular neovascularization.
Lüke
Matthias
M
Institute of Neurophysiology, University of Cologne, Robert-Koch-Strasse 39, 50931 Cologne, Germany. matthias.lueke@med.unituebingen.de
Krott
Ralf
R
Warga
Max
M
Szurman
Peter
P
Grisanti
Salvatore
S
Bartz-Schmidt
Karl Ulrich
KU
Schneider
Toni
T
Lüke
Christoph
C
D000818:Animals; D002417:Cattle; D004359:Drug Therapy, Combination; D004596:Electroretinography / Q000187:drug effects; D019833:Genistein / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000633:toxicity*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012160:Retina / Q000187:drug effects* / Q000502:physiology; D015861:Retinal Neovascularization / Q000517:prevention & control; D013654:Taurine / Q000494:pharmacology*
D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D013654:Taurine; D019833:Genistein; D011505:Protein-Tyrosine Kinases