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Retinal function and histopathology in rabbits treated with Topiramate.

Kjellström, Sten LU ; Bruun, Anitha LU ; Isaksson, Björn ; Eriksson, T ; Andréasson, Sten LU and Ponjavic, Vesna LU (2006) In Documenta Ophthalmologica 113(3). p.179-186
Abstract
Purpose To evaluate retinal function and histopathology in rabbits treated orally with the antiepileptic 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 fullfield ERG demonstrated normal rod function in treated... (More)
Purpose To evaluate retinal function and histopathology in rabbits treated orally with the antiepileptic 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 fullfield 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 antiepileptic drug). (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
rabbit, drug toxicity, immunohistochemistry, topiramate, electroretinogram
in
Documenta Ophthalmologica
volume
113
issue
3
pages
179 - 186
publisher
Springer
external identifiers
  • wos:000242422900005
  • scopus:33751512977
ISSN
1573-2622
DOI
10.1007/s10633-006-9027-8
language
English
LU publication?
yes
id
916960f6-87bb-4931-bcfd-b7189e6e55a1 (old id 163174)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17111186&dopt=Abstract
date added to LUP
2016-04-01 11:42:16
date last changed
2022-01-26 17:00:40
@article{916960f6-87bb-4931-bcfd-b7189e6e55a1,
  abstract     = {{Purpose To evaluate retinal function and histopathology in rabbits treated orally with the antiepileptic 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 fullfield 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 antiepileptic drug).}},
  author       = {{Kjellström, Sten and Bruun, Anitha and Isaksson, Björn and Eriksson, T and Andréasson, Sten and Ponjavic, Vesna}},
  issn         = {{1573-2622}},
  keywords     = {{rabbit; drug toxicity; immunohistochemistry; topiramate; electroretinogram}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{179--186}},
  publisher    = {{Springer}},
  series       = {{Documenta Ophthalmologica}},
  title        = {{Retinal function and histopathology in rabbits treated with Topiramate.}},
  url          = {{https://lup.lub.lu.se/search/files/2603317/625754.pdf}},
  doi          = {{10.1007/s10633-006-9027-8}},
  volume       = {{113}},
  year         = {{2006}},
}