Abstract
Purpose: :
Long-term therapy with the anti-tuberculosis drug ethambutol is known to have neurotoxic effects and cause opticus neuropathy. Our objective was to study the acute toxic effects of ethambutol on the a-wave response of electroretinogram (ERG) of isolated superfused bovine retinas.
Methods: :
Isolated bovine retinas were perfused with phosphate buffered saline (PBS) containing 1mM L-aspartate to block further synaptic transmission in order to record the effects of ethambutol on photoreceptors. After light stimulation electric field potentials were recorded as a transretinal potential using Ag/AgCl-electrodes. Three different light intensities were tested (100 mlux, 1 lux, 10 lux). After reaching a stable ERG amplitude, ethambutol (0.98mM, 3.1 mM und 9.8 mM) was added to the perfusing solution und was perfused for 90 min. Thereafter, ethambutol was washed out during 90 min with PBS containing 1mM L-aspartate. Changes in a-wave amplitude before, during and after ethambutol-application were calculated and plotted.
Results: :
0.98 mM ethambutol did not show any significant effect on the a-wave amplitude at any light-intensity; 3.1 mM ethambutol reduced the a-wave amplitude by 2-folds independent of light-intensity. The inhibition was found to be only partially reversible by washing with PBS containing 1mM L-aspartate, however at lower light-intensities recovery was better (1.4 to 1.65-folds). 9,8 mM ethambutol reduced the a-wave amplitude up to 4-fold, increasing slightly at higher light-intensities. Partial recovery was observed at 100 mlux and 1 lux by washing with PBS containing 1mM L-aspartate; however recovery at 10 lux was minimal.
Conclusions: :
Ethambutol shows dose dependent inhibitory effect on photoreceptors, decreasing the a-wave amplitude with increasing concentration. The inhibition is only partial reversible within the 90-minute washout. Considering the cumulative effect of ethambutol during the long-term therapy, it is essential that the exact dosage is calculated to avoid concentrations that lead to irreversible neuronal damage.
Keywords: electrophysiology: non-clinical • antibiotics/antifungals/antiparasitics • retina