The effects of GABA and vigabatrin on horizontal cell responses to light and the effect of vigabatrin on the electroretinogram.

When used as an antiepileptic drug in humans vigabatrin, which is a GABA analogue and an inhibitor of GABA-aminotransferase, often causes peripheral visual field loss. This could result from increases in endogenous GABA levels. Accordingly we have investigated the effects of GABA on horizontal cells (HCs) of the rabbit retina, and of vigabatrin, when applied for only a few minutes, on HCs and on the electroretinogram (ERG). The intracellular HC and ERG records were first obtained from isolated rabbit retinas during perfusion with a physiological solution. The perfusate was then changed to one containing GABA (2 mM) or vigabatrin (25, 40 or 150 microM) for at least 5 min, and then returned to the control solution. 2 mM GABA significantly but reversibly reduced the light responses of HCs elicited by diffuse light (at -4 log intensity) to 52 +/- 17% (SD, n = 7). Vigabatrin had no significant effect on the light responses of HCs (n = 7), and no effect on the b-wave (n = 4), but the PIII-component of the ERG was slightly but significantly reduced to 84 +/- 5% (SD, n = 5). The high dosage of GABA needed to affect the light responses of HCs could be due to strong GABA uptake systems in the intact rabbit retina. It is, however, possible that in humans receiving long-term treatment with vigabatrin, high levels of GABA occur because of the inhibition of GABA- aminotransferase. It seems, from these observations, that neurons like on-bipolar cells, which are contributors to the b-wave, and HCs are uninfluenced by vigabatrin in short-term experiments. The slightly reduced slow PIII-component, however, indicates an influence on the glial Müller cells which are the main contributors to the slow PIII-component.