Effects of protein tyrosine kinase inhibitor genistein on retinal functionin 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 s tandard solution. The L electroretinogram (ERG) was recorded as a transreti nal potential using silver/silver-chloride electrodes. After recording of s table ERG amplitudes, genistein was added to the solution in different conc entrations. The percentage of b-wave reduction under the drug was calculate d. We also studied the influence of genistein on the a-wave amplitude. Afte r 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 redu ction under the drug was calculated. Concentrations of 3.3 mu Mol/l and higher were found to reduce the b-wave a mplitude. The a-wave amplitude was not changed by the applied concentration s. The ERG only showed toxic effects fi-om genistein beyond concentrations that were found to inhibit endothelial cell growth in vitro. In previous st udies, beneficial effects on trabecular mesh-work cells were present For ge nistein concentrations which are distinctly higher than the maximum nontoxi c 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 app lication of genistein in a sufficient concentration seems possible.