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F. Jammoul, C. Coriat, A. Duboc, M. Simonutti, A.-J. Sahel, S. Picaud, E. Dubus, C. Craft; Pharmacological Neuroprotection of Photoreceptors in Vigabatrin-Treated Animals. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2207.
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The antiepileptic drug, vigabatrin, produces an irreversible constriction of the visual field but is still prescribed for infantile spasms and refractory epilepsy. Retinal damages including retinal dysplasia, cone damages and gliosis were recently described in vigabatrin-treated rats (Duboc et al., 2004). To investigate the cause of these retinal damages, different molecules were administered to vigabatrin-treated animals.
Rats were treated with vigabatrin (200mg/kg) during 65 days. Animals were then sacrificed, the eyes fixed in paraformaldehyde 4% at 4°C overnight to be embedded in OCT for cryostat sectioning after cryopreservation in different sucrose solutions.
In vigabatrin-treated rats, the photopic electroretinogram (ERG) was reduced in amplitude. However, when these animals were daily administered a neuroprotective molecule during the whole treatment, the decrease in ERG amplitude was less important but remained statistically different from those of control animals. On histological sections, the neuroprotective molecule reduced the length of disorganized retinal areas and the difference was statistically significant. Similarly, the number of outer/inner segments from cone photoreceptor was rescued by the neuroprotective molecule. Finally, the extent of lesionned areas that were revealed by the increase in GFAP immunolabelling, was greatly reduced in animals receiving the neuroprotective molecule. Therefore, the treatment reduced all features of the retinal toxicity of vigabatrin.
These results demonstrate that some neuroprotective molecules can limit the vigabatrin-induced retinal lesions. Therefore, these results open the way for understanding the retinal toxicity of vigabatrin and to the evaluation of drug combinations retaining the efficacy of vigabatrin on epilepsy while preserving the retina.
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