Taurine deficiency is a cause of vigabatrin-induced retinal phototoxicity

Authors

  • Firas Jammoul MD,

    1. Institut National de la Sante et de la Recherche Médicale, U592, Institut de la Vision, Paris, France
    2. Université Pierre et Marie Curie-Paris6, UMR-S 592, Paris, France
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    • F.J. and Q.W. contributed equally to this work.

  • Qingping Wang MD,

    1. Institut National de la Sante et de la Recherche Médicale, U592, Institut de la Vision, Paris, France
    2. Université Pierre et Marie Curie-Paris6, UMR-S 592, Paris, France
    3. Ophthalmology Department, Fudan University, Huashan Hospital, Shanghai, China
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    • F.J. and Q.W. contributed equally to this work.

  • Rima Nabbout MD, PhD,

    1. Institut National de la Sante et de la Recherche Médicale, U663, Paris France
    2. University Paris Descartes, Paris France
    3. Assistance Publique-Hopitaux de Paris, Hopital Necker, Service de Neuropédiatrie, Paris, France
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  • Caroline Coriat MD,

    1. Institut National de la Sante et de la Recherche Médicale, U592, Institut de la Vision, Paris, France
    2. Université Pierre et Marie Curie-Paris6, UMR-S 592, Paris, France
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  • Agnès Duboc PhD,

    1. Institut National de la Sante et de la Recherche Médicale, U592, Institut de la Vision, Paris, France
    2. Université Pierre et Marie Curie-Paris6, UMR-S 592, Paris, France
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  • Manuel Simonutti,

    1. Institut National de la Sante et de la Recherche Médicale, U592, Institut de la Vision, Paris, France
    2. Université Pierre et Marie Curie-Paris6, UMR-S 592, Paris, France
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  • Elisabeth Dubus,

    1. Institut National de la Sante et de la Recherche Médicale, U592, Institut de la Vision, Paris, France
    2. Université Pierre et Marie Curie-Paris6, UMR-S 592, Paris, France
    3. Fondation Ophtalmologique Adolphe de Rothschild, Paris France
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  • Cheryl M. Craft PhD,

    1. Departments of Ophthalmology and Cell & Neurobiology, Keck School of Medicine of the University of Southern California, and Mary D. Allen Laboratory for Vision Research, Doheny Eye Institute, Los Angeles, CA
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  • Wen Ye MD,

    1. Ophthalmology Department, Fudan University, Huashan Hospital, Shanghai, China
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  • Stephen D. Collins MD, PhD,

    1. NeuroTherapeutics Pharmaceuticals, Chicago, IL
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  • Olivier Dulac MD,

    1. Institut National de la Sante et de la Recherche Médicale, U663, Paris France
    2. University Paris Descartes, Paris France
    3. Assistance Publique-Hopitaux de Paris, Hopital Necker, Service de Neuropédiatrie, Paris, France
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  • Catherine Chiron MD, PhD,

    1. Institut National de la Sante et de la Recherche Médicale, U663, Paris France
    2. University Paris Descartes, Paris France
    3. Assistance Publique-Hopitaux de Paris, Hopital Necker, Service de Neuropédiatrie, Paris, France
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  • José A. Sahel MD,

    1. Institut National de la Sante et de la Recherche Médicale, U592, Institut de la Vision, Paris, France
    2. Université Pierre et Marie Curie-Paris6, UMR-S 592, Paris, France
    3. Centre Hospitalier National d'Ophtalmologie des quinze-vingts, Paris France
    4. Fondation Ophtalmologique Adolphe de Rothschild, Paris France
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  • Serge Picaud PhD

    Corresponding author
    1. Institut National de la Sante et de la Recherche Médicale, U592, Institut de la Vision, Paris, France
    2. Université Pierre et Marie Curie-Paris6, UMR-S 592, Paris, France
    3. Fondation Ophtalmologique Adolphe de Rothschild, Paris France
    4. Assistance Publique-Hopitaux de Paris, Paris, France
    • INSERM U-592, Institut de la Vision, 17 rue Moreau, 75012 Paris, France
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  • Potential conflict of interest: Nothing to report.

Abstract

Objective

Although vigabatrin irreversibly constricts the visual field, it remains a potent therapy for infantile spasms and a third-line drug for refractory epilepsies. In albino animals, this drug induces a reduction in retinal cell function, retinal disorganization, and cone photoreceptor damage. The objective of this study was to investigate the light dependence of the vigabatrin-elicited retinal toxicity and to screen for molecules preventing this secondary effect of vigabatrin.

Methods

Rats and mice were treated daily with 40 and 3mg vigabatrin, respectively. Retinal cell lesions were demonstrated by assessing cell function with electroretinogram measurements, and quantifying retinal disorganization, gliosis, and cone cell densities.

Results

Vigabatrin-elicited retinal lesions were prevented by maintaining animals in darkness during treatment. Different mechanisms including taurine deficiency were reported to produce such phototoxicity; we therefore measured amino acid plasma levels in vigabatrin-treated animals. Taurine levels were 67% lower in vigabatrin-treated animals than in control animals. Taurine supplementation reduced all components of retinal lesions in both rats and mice. Among six vigabatrin-treated infants, the taurine plasma level was found to be below normal in three patients and undetectable in two patients.

Interpretation

These results indicate that vigabatrin generates a taurine deficiency responsible for its retinal phototoxicity. Future studies will investigate whether cotreatment with taurine and vigabatrin can limit epileptic seizures without inducing the constriction of the visual field. Patients taking vigabatrin could gain immediate benefit from reduced light exposures and dietetic advice on taurine-rich foods. Ann Neurol 2009;65:98–107

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