The effect of GABA and the GABA-uptake-blocker NO-711 on the b-wave of the ERG and the responses of horizontal cells to light.

ABSTRACT

BACKGROUND: The effects of GABA in the retina have now become of special interest because the anti-epileptic drug vigabatrin, a GABA analogue, can cause visual field loss in humans. Vigabatrin inhibits the GABA-aminotransferase, which finally results in GABA accumulation in the extracellular space. The b-wave of the electroretinogram (ERG), which originates partly in on-bipolar cells, is influenced by both GABAergic horizontal cells (HCs) and GABAergic amacrine cells (ACs). Their influences, however, are difficult to separate. In an attempt to isolate the effect of GABAergic ACs, use has been made of the specific effect of the GABA-uptake-blocker NO-711, which blocks only the GABA transporter GAT1 of GABAergic ACs. METHODS: The ERG and the intracellular responses of HCs to light were recorded in the isolated rabbit retina, and the effects of GABA and NO-711, when added separately to the superfusate, were determined. RESULTS: GABA reduced significantly both the light responses of HCs and the b-wave. NO-711 enlarged the b-wave drastically, but did not affect the responses of HCs to light. CONCLUSIONS: An increase in the extracellular GABA concentration decreases the b-wave; an impairment of the function of ACs increases the b-wave. These conditions are discussed in the context of the lack of consistent changes to the b-wave during therapy with vigabatrin.