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


CONCLUSIONS
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.
Jammoul
Firas
F
Institut National de la Sante et de la Recherche Médicale, U592, Institut de la Vision, Paris, France.
Wang
Qingping
Q
Nabbout
Rima
R
Coriat
Caroline
C
Duboc
Agnès
A
Simonutti
Manuel
M
Dubus
Elisabeth
E
Craft
Cheryl M
CM
Ye
Wen
W
Collins
Stephen D
SD
Dulac
Olivier
O
Chiron
Catherine
C
Sahel
José A
JA
Picaud
Serge
S
D000596:Amino Acids / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D002675:Child, Preschool; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography / Q000379:methods; D004791:Enzyme Inhibitors / Q000009:adverse effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007211:Indoles; D007223:Infant; D051379:Mice; D010787:Photosensitivity Disorders / Q000150:complications / Q000188:drug therapy / Q000209:etiology*; D051381:Rats; D012160:Retina / Q000473:pathology; D012164:Retinal Diseases / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D013223:Statistics as Topic; D013654:Taurine / Q000097:blood / Q000172:deficiency* / Q000627:therapeutic use; D020888:Vigabatrin / Q000009:adverse effects* / Q000627:therapeutic use
D000596:Amino Acids; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D013654:Taurine; C007293:DAPI; D020888:Vigabatrin