Effects of protein tyrosine kinase inhibitor genistein on retinal function in superfused vertebrate retina.
The aim of this study was to evaluate safe concentrations of genistein for a potential intraocular application using the isolated retina technique on bovine retina preparations. Bovine retinas were isolated and perfused with an oxygen pre-equilibrated standard solution. The electroretinogram (ERG) was recorded as a transretinal potential using silver/silver-chloride electrodes. After recording of stable ERG amplitudes, genistein was added to the solution in different concentrations. The percentage of b-wave reduction under the drug was calculated. We also studied the influence of genistein on the a-wave amplitude. After the addition of aspartate, the b-wave amplitude was reduced continuously until unmasked a-wave amplitudes were reached. Genistein was then added to the aspartate containing perfusate. The percentage of a-wave amplitude reduction under the drug was calculated. Concentrations of 3.3 microMol/l and higher were found to reduce the b-wave amplitude. The a-wave amplitude was not changed by the applied concentrations. The ERG only showed toxic effects from genistein beyond concentrations that were found to inhibit endothelial cell growth in vitro. In previous studies, beneficial effects on trabecular meshwork cells were present for genistein concentrations which are distinctly higher than the maximum nontoxic concentration reported here. It was shown that the photoreceptor layer is not affected at the examined concentration range. Therefore, we attribute the toxic effects to postsynaptic interaction of genistein. Intraocular application of genistein in a sufficient concentration seems possible.
Lüke
C
C
Department of Ophthalmology, University of Cologne, Germany. aia18@uni-koeln.de
Krott
R
R
Lüke
M
M
Lebek
J
J
Walter
P
P
Brunner
R
R
Sickel
W
W
D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D002417:Cattle; D004596:Electroretinography / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012160:Retina / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D001224:Aspartic Acid; D019833:Genistein; D011505:Protein-Tyrosine Kinases