Acute Vigabatrin Retinotoxicity in Albino Rats Depends on Light But Not GABA

Abstract

Summary:Purpose: Vigabatrin (VGB) is an irreversible inhibitor of γ -aminobutyric acid (GABA) transaminase. Its use as an antiepileptic drug (AED) has been limited because it causes retinal dysfunction, leading to visual field defects (VFDs). We performed this study to identify factors contributing to acute VGB retinotoxicity.Methods: In ex vivo experiments, Sprague-Dawley rat retinas were isolated and incubated with VGB or GABA in the presence or absence of light. In in vivo experiments, Sprague-Dawley rats were given intraperitoneal injections of VGB and then exposed to light or kept in the dark. The retinas were analyzed histologically by using both light and electron microscopy.Results: Incubating retinas with 50-500 µM VGB under 20,000 Lux white light for ≤20 h caused a characteristic time-and dose-dependent degeneration limited to the outer retina. Incubating retinas with 500 µM VGB in darkness for 20 h caused no damage. Five hundred micromolar GABA and 50 µM tiagabine were not toxic in the presence or absence of light. Sprague-Dawley rats exposed to an intense white light for 20 h after a 1,000-mg/kg intraperitoneal injection of VGB showed damage in the outer retina, whereas those kept in the dark did not.Conclusions: Direct exposure of the retina to VGB causes acute retinotoxicity that depends on light exposure rather than GABA accumulation.

The Vigabatrin Induced Retinal Toxicity is Associated with Photopic Exposure and Taurine Deficiency: An In Vivo Study

“…Subsequent morphological studies have described the disorganized ONL, shortened inner and outer cone segments, as well as the disrupted RGCs layer [13,14]. The VGB-elicited photoreceptor degeneration is reported to be light dependent [25,26]. However, these results are mainly harvested from histological and immunochemistry observations of fixed tissues.…”

Recent Advances in the Pharmacotherapy of Infantile Spasms

“…One study in rodents showed that vigabatrin-associated retinopathy is associated with light exposure [72]. More recently, it has been suggested that a deficiency of taurine is implicated in the pathogenic process of vigabatrinassociated retinopathy [73,74].…”

Dose-related changes in retinal function and PKC-alpha expression in rabbits on vigabatrin medication

“…Alterations of Müller cell morphology have been detected previously, in rabbits, during vigabatrin medication in a study by Ponjavic et al [37]. Changes in the ONL and OLM in rats on VGB medication are described by Izumi et al [40], who also suggest Müller cell dysfunction as well as photoreceptor damage as a result of exposition to VGB in combination with light, rather than as an effect of raised concentrations of GABA in the retina. In rats [39], increased GFAP immunoactivity has been interpreted as an indicator of VGB-induced Müller cell activation and gliosis formation.…”

“…Similar results are shown by Duboc et al [39], revealing ff-ERG alterations and morphological changes in Müller cells in rats. Duboc et al [39] as well as Izumi et al [40] have also shown cone photoreceptor damage in rats treated with VGB. The main goal of the present study was to further investigate the role of the drug dose in VGB-induced toxic retinopathy, functionally measured by ff-ERG.…”