Retinal function and histopathology in rabbits treated with Topiramate.
OBJECTIVE
To evaluate retinal function and histopathology in rabbits treated orally with the anti-epileptic drug topiramate.


METHODS
Six rabbits were treated with a daily oral dose of topiramate during a period of eight months. Six rabbits receiving water served as controls. Blood samples were analyzed for determination of topiramate serum levels in order to ensure successful drug exposition. Standardized full-field electroretinograms (ERGs) were performed before treatment and then at 2, 3 and 8 months during the treatment period. After terminating treatment the rabbits were sacrificed and the morphology of the sectioned retina was studied.


RESULTS
After eight months of treatment the full-field ERG demonstrated normal rod function in treated and control rabbits, but the light adapted 30 Hz flicker b-wave amplitude was significantly reduced in the treated rabbits. This was the case for both the light adapted (Wilcoxon signed ranks test, P = 0.046) and the dark adapted (Wilcoxon signed ranks test, P = 0.028) 30 Hz flicker response from the treated rabbits. Retinal immunohistology revealed a severe accumulation of GABA in amacrine cells and in the inner plexiform layer in 4 of 6 treated rabbits compared to the controls.


CONCLUSIONS
Topiramate, orally administrated to rabbits, may cause a significant reduction of the retinal function demonstrated by the reduced b-wave amplitude in the full-field ERG, as well as changes in immunohistology characterized by a severe accumulation of GABA in the inner retina. The retinal dysfunction and the morphological changes indicate that topiramat may damage the retina, similarly to vigabatrin (another anti-epileptic drug).
Kjellström
S
S
Department of Ophthalmology, University of Lund, S 221 85, Lund, Sweden.
Bruun
A
A
Isaksson
B
B
Eriksson
T
T
Andréasson
S
S
Ponjavic
V
V
D000221:Adaptation, Ocular; D000284:Administration, Oral; D025042:Amacrine Cells / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D003623:Dark Adaptation; D004334:Drug Administration Schedule; D004596:Electroretinography; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007150:Immunohistochemistry; D010775:Photic Stimulation / Q000379:methods; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D014018:Tissue Distribution; D000077236:Topiramate; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose; D005680:gamma-Aminobutyric Acid