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U. Kjellstrom, S. Kjellstrom, A. Bruun, S. Andréasson, V. Ponjavic; Evaluation of Retinal Function and Morphology in Rabbits Several Months After Terminating Treatment With Vigabatrin . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3946.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have previously reported changes in retinal function and morphology in rabbits treated with vigabatrin. The purpose of the present study was to evaluate retinal function and morphology several months after terminating a year long treatment with vigabatrin. Methods: Seven rabbits were treated with a daily per oral dose of vigabatrin during 11–14 months. After terminating treatment an observation period of 4–7 months followed. Nine rabbits receiving water served as controls. Two treated rabbits and three controls died unexpectedly and randomly during the study, and were therefore excluded. Standardized full–field electroretinograms (ERGs) were assessed 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 of retinal sections were GABA, GFAP, GAD and vimentin. Blood samples were analyzed on several occasions prior to and during treatment, for determination of vigabatrin serum concentration, in order to ensure successful drug administration. Results: After 11–14 months of treatment the standardized full–field ERG was reduced in all five rabbits treated with vigabatrin. There was a statistically significant difference in the dark adapted cone b–wave amplitude between the treated animals and the controls (Wilcoxon signed ranks test, p=0.043). This difference was consistent also 4–7 months after terminating treatment. Immunohistology of the sectioned retina did not demonstrate any difference between the treated animals and the controls. There was no significant difference in immunoreactivity for the four different antibodies between the treated animals and the controls. One of the treated animals had a slightly enhanced GFAP immunoreactivity, but this was also seen in one of the controls. In all treated rabbits the serum analyses demonstrated elevated drug levels. Conclusions: Several months after terminating treatment with vigabatrin the rabbit full–field ERG remains reduced in cone b–wave amplitude indicating that vigabatrin induced retinal dysfunction is irreversible. However, immunohistology of the inner retina and the glial cells is normal after a period without treatment, implying that the previously reported changes in retinal morphology and glial cell activity are reversible, and probably exist only during treatment.
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