Vigabatrin (Sabril), an Anti-Epileptic Drug, Induces ERG Alteration and Retinal Morphology Change in Rat

Abstract

Abstract: : Vigabatrin (GVG), an effective inhibitor of GABA-transaminase, is an anti-epileptic drug which induces an irreversible constriction of peripheral visual field in treated humans patients. Purpose: To determine the origin of GVG retinal toxicity on the rat retina. Methods: 20 rats were daily injected intraperitonealy with vigabatrin (GVG) during 45 days, stopped 2 or 43 days prior to electroretinogram (ERG) testing, after rats were sacrified and the retinal morphology was investigated by immunological techniques. Results: The treatment had no effect on rod function, but induced a significant and irreversible decrease of photopic and flicker ERG amplitudes at the time recovery, suggesting a functional alteration of cone photoreceptor pathway. The oscillatory potentials were also decreased. Histological sections showed peripheral photoreceptor dysplasia with photoreceptor nuclei in contact with the retinal pigment epithelium (RPE). These disturbed outer nuclear layer (ONL) contained displaced glial cells, and these cells expressed GFAP in the entire retina. Only the outer nuclear layer appear altered by GVG treatment. In normal ONL areas, photoreceptor degeneration was attested by TUNEL-staining and active caspase3 immunocytochemistry. Cone photoreceptor quantification further confirmed a significant 17,7 (2 days) and 21 % (43 days) reduction in cell number. Conclusions: In the retina, GVG treatment seems to induce cone degeneration as indicated by cell counting and functional testing. These result were in accord with the ERG defects observed in humans. These animal model should provide some clues on the molecular mechanisms leading to the visual field constriction in epileptic patients treated with GVG.

Keywords: drug toxicity/drug effects • degenerations/dystrophies • inhibitory neurotransmitters