Download The retinal toxicity of an antiepileptic drug blocking the GABA

The retinal toxicity of an antiepileptic drug blocking the GABAtransaminase: GABA excitotoxicity or taurine deficiency?
Serge Picaud, Institut de la Vision, Paris
By contrast to brain structures, GABA, the main inhibitory neurotransmitter,
remains excitatory in the adult retinal network. Furthermore, it can activate
GABAc receptors, which do not desensitize and thus generate large sustained
responses. These specificities could explain the retinal toxicity of vigabatrin,
an anti-epileptic drug. Indeed, this drug blocks the GABA-transaminase and
thus increases up to 5 fold the retinal GABA concentration. In patients, it was
found to generate an irreversible constriction of the visual field. Despite this
major secondary effect, the damaging consequences of seizures and the drug
efficacy were such that the vigabatrin (sabril) remains the first line drug for
the treatment of infantile spasms and a third line drug for some forms of
epilepsy in adults.
The presentation will describe our recent work on GABA function at
photoreceptor terminals and its implication in photoreceptor toxicity. In
particular, we will present how we elucidated the mechanism of vigabatrinelicited photoreceptor toxicity. Finally, we will discuss different strategies to
prevent the retinal toxicity of the anti-epileptic drug and future treatments.