Original Article

Taurine deficiency is a cause of vigabatrin-induced retinal phototoxicity†

  1. Firas Jammoul MD1,2,‡,
  2. Qingping Wang MD1,2,3,‡,
  3. Rima Nabbout MD, PhD4,5,6,
  4. Caroline Coriat MD1,2,
  5. Agnès Duboc PhD1,2,
  6. Manuel Simonutti1,2,
  7. Elisabeth Dubus1,2,10,
  8. Cheryl M. Craft PhD7,
  9. Wen Ye MD3,
  10. Stephen D. Collins MD, PhD8,
  11. Olivier Dulac MD4,5,6,
  12. Catherine Chiron MD, PhD4,5,6,
  13. José A. Sahel MD1,2,9,10,
  14. Serge Picaud PhD1,2,10,11,*

Article first published online: 4 FEB 2009

DOI: 10.1002/ana.21526

Issue

Annals of Neurology

Annals of Neurology

Volume 65, Issue 1, pages 98–107, January 2009

Additional Information

How to Cite

Jammoul, F., Wang, Q., Nabbout, R., Coriat, C., Duboc, A., Simonutti, M., Dubus, E., Craft, C. M., Ye, W., Collins, S. D., Dulac, O., Chiron, C., Sahel, J. A. and Picaud, S. (2009), Taurine deficiency is a cause of vigabatrin-induced retinal phototoxicity. Annals of Neurology, 65: 98–107. doi: 10.1002/ana.21526

Author Information

  1. 1

    Institut National de la Sante et de la Recherche Médicale, U592, Institut de la Vision, Paris, France

  2. 2

    Université Pierre et Marie Curie-Paris6, UMR-S 592, Paris, France

  3. 3

    Ophthalmology Department, Fudan University, Huashan Hospital, Shanghai, China

  4. 4

    Institut National de la Sante et de la Recherche Médicale, U663, Paris France

  5. 5

    University Paris Descartes, Paris France

  6. 6

    Assistance Publique-Hopitaux de Paris, Hopital Necker, Service de Neuropédiatrie, Paris, France

  7. 7

    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

  8. 8

    NeuroTherapeutics Pharmaceuticals, Chicago, IL

  9. 9

    Centre Hospitalier National d'Ophtalmologie des quinze-vingts, Paris France

  10. 10

    Fondation Ophtalmologique Adolphe de Rothschild, Paris France

  11. 11

    Assistance Publique-Hopitaux de Paris, Paris, France

  1. ‡

    F.J. and Q.W. contributed equally to this work.

*INSERM U-592, Institut de la Vision, 17 rue Moreau, 75012 Paris, France

  1. †

    Potential conflict of interest: Nothing to report.

Publication History

  1. Issue published online: 12 FEB 2009
  2. Article first published online: 4 FEB 2009
  3. Manuscript Accepted: 18 AUG 2008
  4. Manuscript Revised: 25 JUL 2008
  5. Manuscript Received: 5 JUN 2008

Funded by

  • Institut National de la Sante et de la Recherche Médicale
  • Université Pierre et Marie Curie (Paris VI)
  • Fondation Ophtalmologique A. de Rothschild (Paris)
  • Agence Nationale pour la Recherche (ANR: GABARET)
  • Fédération des Aveugles de France
  • European Economic Community. Grant Number: EVI-GENORET-512036
  • Ovation Pharmaceuticals (USA)
  • Fellowship from the city of Paris
  • University of Tichcrine (Syria;
  • Mary D. Allen Laboratory for Vision Research
  • Doheny Eye Institute (DEI)
  • NIH National Eye Institute (NEI). Grant Numbers: EY015851, EY03040 [DEI Core Grant]
  • RPB

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (1609K)

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

View Full Article (HTML) Get PDF (1609K)