Epilepsie ou malvoyance : la taurine pour ne plus avoir choisir

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Epilepsie ou malvoyance la taurine pour ne plus
avoir à choisir !
Jammoul, Wang, Coriat, Duboc, Paques, Hanoteau,
Simonutti, Rudolf, Roux, Nehlig, José Sahel and
Serge Picaud Institut de la Vision UPMC, INSERM
UMR-S 968, CNRS UMR 7210 Paris serge.picaud_at_ins
erm.fr
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Lateral inhibition by horizontal cells

• Contrast enhancement
• Local averaging of light intensities

?
?
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All components of a GABA synapse
Des récepteurs GABAA et GABAC
GABA-R ?2 subunit mRNA
GABAA et GABAC
(Picaud et al., 1998) (Pattnaik et al., 2000)
Le transporteur vésiculaire du GABA
GAD 65 mRNA
VIAAT
(Jellali et al., 2001)
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Retinal toxicity of vigabatrin (Sabril)

• Decrease amplitude
• in the photopic ERG

• Visual field constriction

Control
GVG
Control
Vigabatrin

• EOG alteration

• Toujours prescrit dans le spasme infantile
• et les épilepsies réfractaires

GVG
OFF
Control
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Augmentation du GABA rétinien par le vigabatrin
GABA
Vigabatrin
GABA
DAPI
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Photopic ERG cone pathway

• Adult rats
• daily Intraperitoneal injection 250mg/Kg 45 days
• Recovery 2 or 43 days

45 day treated rat
Amplitude (µV)
Control
Vigabatrin
250
1cdsm-2
200


25 cdsm-2
150
SSS
100
SSS

50 µV
30 msec
50
SSS
0
1
3
25
flash intensity (cdsm-2)
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Peripheral retinal damage
Control
Vigabatrin
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In vivo examination of lesions in rats Clinical
trial starting in patients
EM
Autofluorescence
SLO reflexion
SLO Autofluorescence
SLO reflexion
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General cone damage
Control
Vigabatrin
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Ectopic of rod synapses
cones ON Bipolar cells
Bassoon/PKC
Go/Vglut1
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The main hypothesis Retinal phototoxicity Only
in albino animals
Control Darkness
VGV 500µM Darkness
Control 20 000lux
VGV 500µM 20 000 lux
GABA 500µM 20 000 lux, 20h
(Izumi et al., 2004)
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Darkness prevents all retinal lesions vigabatrin-
elicited plasticity
Control
Vigabatrin light
Vigabatrin in darkness
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Amino acid blood levels Taurine decrease
Taurine
Glutamate
VGB
COOH
400
NH2
GABA
300
COOH
µmol/l

200
Taurine

100
SOOOH
0
Ctrol
VGB
Ctrol
VGB
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Taurine deficiency is known to induce
photoreceptor degeneration
12 months
Lesion Topography and New Histological Features
in FelineTaurine Deficiency Retinopathy LEON,A.,
LEVICK W. R., SAROSSY M. G.
Exp. Eye Res. (1995) 61, 731-741
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Taurine supplementation decreases retinal lesions
control
VGB
VGB taurine
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Clinical relevance of taurine deficiency in
VGB-treated infants
und undetectable SD Standard Deviation
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Conclusions

• All components of GABA transmission at cone
  terminals
• Vigabatrin induces cone photoreceptor damage,
  neuronal plasticity and gliosis
• SLO can be used to visualize in vivo the
  photoreceptor layer disorganization
• Retinal lesions are due to an induced
  phototoxicity
• Patients should limit bright light exposure
• Vigabatrin treatment lead to a decrease in
  taurine plasma level
• Taurine supplementation can limit the
  vigabatrin-elicited retinal toxicity
• A combination vigabatrin/taurine will be
  developped for safe treatment of epilepsy and
  infantile spasms

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Qingping WANG Agnès DUBOC Firas JAMMOUL Caroline
CORIAT Noëlle HANOTEAU Abdeljelil JELLALI Michel
ROUX Manuel SIMONUTTI Valérie FORSTER Elisabeth
DUBUS Michel PAQUES José SAHEL INSERM
U-450 Gabrielle RUDOLF Astrid NEHLIG
Acknowledgments
Strasbourg Paris
Grants INSERM, UMPC-Paris6, Fédération des
aveugles de France, IRRP, European Commission
(GENORET-512036 ), Ville de Paris, AP-HP, ANR
(GABARET), Ovation Pharmaceuticals
University of southern California Cheryl CRAFT