1. Acute vigabatrin retinotoxicity in albino rats depends on light but not GABA.
- Author
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Izumi Y, Ishikawa M, Benz AM, Izumi M, Zorumski CF, and Thio LL
- Subjects
- Acute Disease, Animals, Darkness adverse effects, Male, Nipecotic Acids toxicity, Photoreceptor Cells pathology, Rats, Rats, Sprague-Dawley, Retina pathology, Retinal Diseases pathology, Scotoma chemically induced, Scotoma pathology, Tiagabine, Vision Disorders pathology, Visual Fields drug effects, Anticonvulsants toxicity, Light adverse effects, Photic Stimulation adverse effects, Retina drug effects, Retinal Diseases chemically induced, Vigabatrin toxicity, Vision Disorders chemically induced, gamma-Aminobutyric Acid physiology
- Abstract
Purpose: Vigabatrin (VGB) is an irreversible inhibitor of gamma-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 microM VGB under 20,000 Lux white light for < or = 20 h caused a characteristic time- and dose-dependent degeneration limited to the outer retina. Incubating retinas with 500 microM VGB in darkness for 20 h caused no damage. Five hundred micromolar GABA and 50 microM 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., (Copyright 2004 International League Against Epilepsy)
- Published
- 2004
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