Retinal function in rabbits does not improve 4-5 months after terminating treatment with vigabatrin.
OBJECTIVE
We have previously reported changes in retinal function and histopathology in rabbits treated with vigabatrin. The purpose of the present study was to evaluate retinal function and histopathology of retina in rabbits 4-5 months after terminating vigabatrin medication.


METHODS
Five rabbits were treated with a daily per oral dose of vigabatrin during 12-13 months. After terminating treatment an observation period of 4-5 months followed. Six rabbits receiving water served as controls. Standardized full-field electroretinograms were performed every 6-8 weeks, using a Burian-Allen bipolar contact lens. After 18 months the rabbits were sacrificed and the morphology of the sectioned retina was studied. The antibodies used for staining were GABA, GFAP, GAD, and vimentin.


RESULTS
After 12-13 months of treatment the full-field ERG was reduced in all rabbits treated with vigabatrin. There was a statistically significant difference in the dark adapted cone b-wave amplitude between treated animals and controls (Wilcoxon signed-rank test, p = 0.043). This difference was consistent also 4-5 months after terminating treatment. Immunohistology of the sectioned retina demonstrated no significant difference in immunoreactivity between treated animals and controls. All treated rabbits demonstrated elevated serum concentration of the drug during medication.


CONCLUSIONS
Four to five months after terminating treatment with vigabatrin the rabbit full-field ERG remains reduced in isolated cone b-wave amplitude indicating that vigabatrin induced retinal dysfunction may be irreversible. However, immunohistology is normal after a period without treatment, implying that the previously described changes in retinal morphology and glial cell activity are reversible, and probably exist only during treatment.
Kjellström
Ulrika
U
Dept. of Ophthalmology, University of Lund, Lund, S 221 85, Sweden. ulrika.kjellstrom@skane.se
Kjellström
Sten
S
Bruun
Anitha
A
Andréasson
Sten
S
Ponjavic
Vesna
V
D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004596:Electroretinography / Q000187:drug effects; D005500:Follow-Up Studies; D011817:Rabbits; D012160:Retina / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D012640:Seizures / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D020888:Vigabatrin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014794:Visual Fields / Q000187:drug effects / Q000502:physiology*
D000927:Anticonvulsants; D020888:Vigabatrin