Abstract
Purpose :
In our previous studies we found out that chloroquine and hydroxychloroquine at the concentrations of 160 and 190 µM respectively didn't show a toxic effect on the a-wave amplitude of the electroretinogram (ERG) of isolated superfused bovine retinas. In our present work our objective was to find out, if these substances at the same or lower concentration would show inhibitory effect on the b-wave of the ERG, to compare the volnerability of retinal layers, photoreceptors and inner nuclear, towards these drugs.
Methods :
Isolated bovine retinae were mounted in a temperature-controlled recording chamber and were perfused with an oxygen-saturated standard solution. Electric field potentials were recorded using Ag/AgCl-electrodes, to obtain the electroretinogram after each flash of light. After reaching stable ERG conditions, chloroquine or hydroxychloroquine were added for 90 minutes. Thereupon, the drugs were washed out during 90 min reperfusion with the standard solution. The changes of a-/b-wave amplitude before, during and after drug application were calculated and plotted. In the b-wave experiments 160, 48, 16 µM chloroquine and 190, 19 µM hydroxychloroquine concentrations were used.
Results :
Application of chloroquine (160 µM) and hydroxychloroquine (190 µM) didn't decrease the a-wave amplitude (n=6). In the b-wave experiments chloroquine almost completely blocked the ERG responce at the same concentration (160 µM), with very low recovery after wash-out (n=3). Even through lower dosis of chloroquine 48 µM (n=3) and 16 µM (n=3) the b-wave amplitude was significantly decreased, 3,5 and 2,5 folds respectively, the recovery of the b-wave amplitude after drug removal at 16 µM concentration was complete, at 48 µM only partial (2 folds). 190 µM hydroxychloroquine also almost completely erased the b-wave, with minimal recovery after wash-out (n=3). At 10 times lower concentration, 19 µM (n=3), the inhibiton was still observed (3 folds), after wash-out the amplitude rates returned to initial level.
Conclusions :
In a superfused vertebrate retina assay chloroquine and hydroxychloroquine showed a clearly stronger inhibiton of the b-wave, than of the a-wave ERG amplitude, even when the concentration of the substance was 10 times lower, showing a higher volnerability of retinal nuclear layer to the toxic effect of these drugs, compared to photoreceptors.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.