Purpose:Vigabatrin (VGA, Sabril™), a structural analog of gamma-aminobutyric acid, is an irreversible inhibitor of gamma-aminobutyric acid transaminase. Because of its effects on GABA accumulation in the extracellular space, VGA is being developed as an antiepileptic agent for drug-resistant seizures. Oculotoxicity of VGA was first characterized as visual field defects. VGA may also induce optic nerve atrophy and it has recently been shown that VGA induces apoptosis in photoreceptors.
Methods: Using an ex vivo rat retinal preparation, we examined retinotoxic effects of VGA.
Results:Incubation of retinal segments with 500 µM VGA for 20 hours in dark did not reveal apparent retinal degeneration. In contrast, incubation under white light (40000 Lux) revealed a characteristic degeneration limited to the outer nuclear layer and the outer segments of photoreceptor cells. Inner retinal layers were intact. Although it was hypothesized that the damage resulted from accumulation of GABA, 500 µM GABA under the same light did not induce phototoxicity. When rats were exposed to an intense light for 20 hours, intraperitoneal injection of VGA did not mimic the damage observed in this ex vivo study but revealed irregularity of the outer limiting membrane resulting in the development of a wavy appearance in the outer nuclear layer. These observations indicate that VGA’s oculotoxicity is acute when the retina is exposed to light.
Conclusions:Exposure to sunlight would be particularly toxic for patients treated with VGA.