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Retinal function and histopathology in rabbits treated with Topiramate

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Abstract

Purpose

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).

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Acknowledgements

We thank Ing-Marie Holst and Boel Nilsson for skillful technical assistance. This study was supported by grants from Stiftelsen Synfrämjandets Forskningsfond, Kronprinsessans Margaretas Arbetsnämnd, the Swedish Medical Research Council (project no. 73X-12597-03A), the 2nd ONCE international award for new technologies for the blind and the Faculty of Medicine at the University of Lund.

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Authors and Affiliations

  1. Department of Ophthalmology, University of Lund, S 221 85, Lund, Sweden

    S. Kjellström, A. Bruun, S. Andréasson & V. Ponjavic

  2. Hospital Pharmacy, University of Lund, Lund, Sweden

    B. Isaksson & T. Eriksson

Authors
  1. S. Kjellström
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  2. A. Bruun
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  3. B. Isaksson
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  4. T. Eriksson
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  5. S. Andréasson
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  6. V. Ponjavic
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Correspondence to V. Ponjavic.

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Kjellström, S., Bruun, A., Isaksson, B. et al. Retinal function and histopathology in rabbits treated with Topiramate. Doc Ophthalmol 113, 179–186 (2006). https://doi.org/10.1007/s10633-006-9027-8

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