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Taurine deficiency is a cause of vigabatrin‐induced retinal phototoxicity
Author(s) -
Jammoul Firas,
Wang Qingping,
Nabbout Rima,
Coriat Caroline,
Duboc Agnès,
Simonutti Manuel,
Dubus Elisabeth,
Craft Cheryl M.,
Ye Wen,
Collins Stephen D.,
Dulac Olivier,
Chiron Catherine,
Sahel José A.,
Picaud Serge
Publication year - 2009
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21526
Subject(s) - vigabatrin , retinal , taurine , phototoxicity , retina , electroretinography , retinal ganglion cell , medicine , endocrinology , pharmacology , anticonvulsant , biology , ophthalmology , epilepsy , neuroscience , biochemistry , psychiatry , amino acid , in vitro
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