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Alterations in electroretinograms and retinal morphology in rabbits treated with vigabatrin

Ponjavic, Vesna LU ; Gränse, Lotta LU ; Kjellström, Sten LU ; Andréasson, Sten LU and Bruun, Anitha LU (2004) In Documenta Ophthalmologica 108(2). p.125-133
Abstract

PURPOSE: To determine whether long-term treatment with the anti-epileptic drug vigabatrin causes damage to rabbit retina.

METHODS: Five rabbits were treated continuously with a daily dose of vigabatrin solution per orally during a period of 1-8 months. Two rabbits receiving water were used as controls. Repeated full-field electroretinograms (every two weeks) were assessed during this period. Vigabatrin serum concentration was repeatedly measured for securing successful drug administration. After termination of treatment the rabbits were sacrificed and the morphology of the sectioned retina was studied.

RESULTS: In all rabbits treated with vigabatrin the serum analyses repeatedly demonstrated elevated drug concentration.... (More)

PURPOSE: To determine whether long-term treatment with the anti-epileptic drug vigabatrin causes damage to rabbit retina.

METHODS: Five rabbits were treated continuously with a daily dose of vigabatrin solution per orally during a period of 1-8 months. Two rabbits receiving water were used as controls. Repeated full-field electroretinograms (every two weeks) were assessed during this period. Vigabatrin serum concentration was repeatedly measured for securing successful drug administration. After termination of treatment the rabbits were sacrificed and the morphology of the sectioned retina was studied.

RESULTS: In all rabbits treated with vigabatrin the serum analyses repeatedly demonstrated elevated drug concentration. Full-field electroretinograms demonstrated normal rod function in all treated rabbits, but reduced cone function in two of the five treated rabbits verified by 30Hz flicker stimulation. Morphologic studies of the sectioned retina demonstrated GFAP immunoactivity of the glial cells localized in the retinal periphery in all five treated rabbits, one of which had staining also in the centrally localized glial cells. The treated rabbits also demonstrated a weaker GAD staining in the IPL and less positive amacrine cells, compared to the controls. Only two treated rabbits had normal GABA staining while three had an enhanced GABA immunoreactivity and undistinguishable fibers in the IPL. In three out of five treated rabbits the Müller cells were short, stubby and fragmented, with swollen endfeet.

CONCLUSION: This study demonstrates changes in histopathology caused by vigabatrin in an animal model, which has not been reported previously. We have found that vigabatrin orally administrated to rabbits does not affect rod function but may reduce cone function in the full-field electroretinogram, which is similar to the previously reported vigabatrin effect on the human ERG. The results indicate that vigabatrin may damage or influence, at least one cell type in the rabbit retina.

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subject
keywords
Animals, Anticonvulsants, Electroretinography, Glial Fibrillary Acidic Protein, Glutamate Decarboxylase, Rabbits, Retina, Vigabatrin, Vimentin, gamma-Aminobutyric Acid, Journal Article, Research Support, Non-U.S. Gov't
in
Documenta Ophthalmologica
volume
108
issue
2
pages
9 pages
publisher
Springer
external identifiers
  • wos:000223605400003
  • pmid:15455795
  • scopus:4344610320
ISSN
1573-2622
DOI
10.1023/B:DOOP.0000036780.96560.74
language
English
LU publication?
yes
id
3a9beb5f-01cc-42f9-a34e-4932a7efe4da (old id 130000)
alternative location
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=15455795&dopt=Abstract
date added to LUP
2007-07-09 10:22:35
date last changed
2017-04-18 09:51:15
@article{3a9beb5f-01cc-42f9-a34e-4932a7efe4da,
  abstract     = {<p>PURPOSE: To determine whether long-term treatment with the anti-epileptic drug vigabatrin causes damage to rabbit retina.</p><p>METHODS: Five rabbits were treated continuously with a daily dose of vigabatrin solution per orally during a period of 1-8 months. Two rabbits receiving water were used as controls. Repeated full-field electroretinograms (every two weeks) were assessed during this period. Vigabatrin serum concentration was repeatedly measured for securing successful drug administration. After termination of treatment the rabbits were sacrificed and the morphology of the sectioned retina was studied.</p><p>RESULTS: In all rabbits treated with vigabatrin the serum analyses repeatedly demonstrated elevated drug concentration. Full-field electroretinograms demonstrated normal rod function in all treated rabbits, but reduced cone function in two of the five treated rabbits verified by 30Hz flicker stimulation. Morphologic studies of the sectioned retina demonstrated GFAP immunoactivity of the glial cells localized in the retinal periphery in all five treated rabbits, one of which had staining also in the centrally localized glial cells. The treated rabbits also demonstrated a weaker GAD staining in the IPL and less positive amacrine cells, compared to the controls. Only two treated rabbits had normal GABA staining while three had an enhanced GABA immunoreactivity and undistinguishable fibers in the IPL. In three out of five treated rabbits the Müller cells were short, stubby and fragmented, with swollen endfeet.</p><p>CONCLUSION: This study demonstrates changes in histopathology caused by vigabatrin in an animal model, which has not been reported previously. We have found that vigabatrin orally administrated to rabbits does not affect rod function but may reduce cone function in the full-field electroretinogram, which is similar to the previously reported vigabatrin effect on the human ERG. The results indicate that vigabatrin may damage or influence, at least one cell type in the rabbit retina.</p>},
  author       = {Ponjavic, Vesna and Gränse, Lotta and Kjellström, Sten and Andréasson, Sten and Bruun, Anitha},
  issn         = {1573-2622},
  keyword      = {Animals,Anticonvulsants,Electroretinography,Glial Fibrillary Acidic Protein,Glutamate Decarboxylase,Rabbits,Retina,Vigabatrin,Vimentin,gamma-Aminobutyric Acid,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {2},
  pages        = {125--133},
  publisher    = {Springer},
  series       = {Documenta Ophthalmologica},
  title        = {Alterations in electroretinograms and retinal morphology in rabbits treated with vigabatrin},
  url          = {http://dx.doi.org/10.1023/B:DOOP.0000036780.96560.74},
  volume       = {108},
  year         = {2004},
}