Vigabatrin, the gaba-tranaminae inhibitor, damage cone photoreceptor in rat

In epilepy, enhancing GABAinhibitory neurotranmiion ha become a major therapeutic trategy to limit the occurrence of eizure. Vigabatrin (which block the GABA tranaminae, the GABA degrading enzyme) i a very efficient drug for the treatment of partial epilepy, pharmacoreitant epilepy and infantile pam. Unfortunately, long term VGBadminitration reulted in irreverible viual field contriction in approximately 40% of patient. Thi viual lo i aociated with a dyfunction in the cone photoreceptor pathway more than in the rod pathway. To invetigate the cellular origin of VGB toxicity, the author treated rat daily with VGB for 45 day. Two day after arreting thi treatment, rat exhibited an irreverible decreae in the photopic electroretinogram, the flicker repone, and the ocillatory potential. Thee functional alteration were aociated with a peripheral diorganization of the outer retina. However, photoreceptor damage wa not limited to thee diorganized area, but cone inner and outer egment were everely injured in more central area and their number were irreveribly decreaed by 17 to 20%. Ultratructural examination of the retina confirmed the preence of major photoreceptor damage, which were further upported by terminal deoxynucleotidyltranferae-mediated dUTP nick end labeling (TUNEL) and capae-3 activation both indicative of photoreceptor apoptoi. Thi tudy ugget that the viual field lo in vigabatrin-treated epileptic patient may reult from a equence of event tarting from cone cell injury to a more evere diorganization of the photoreceptor layer.—Valerie Bioue