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Dose-related changes in retinal function and PKC-alpha expression in rabbits on vigabatrin medication

Authors
  • Kjellström, Ulrika1
  • Bruun, Anitha1
  • Ghosh, Fredrik1
  • Andréasson, Sten1
  • Ponjavic, Vesna1
  • 1 University of Lund, Department of Ophthalmology, Lund, 221 85, Sweden , Lund (Sweden)
Type
Published Article
Journal
Graefe's Archive for Clinical and Experimental Ophthalmology
Publisher
Springer-Verlag
Publication Date
May 03, 2009
Volume
247
Issue
8
Pages
1057–1067
Identifiers
DOI: 10.1007/s00417-009-1093-7
Source
Springer Nature
Keywords
License
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Abstract

BackgroundTo investigate, in a rabbit model, the effect of two different doses of vigabatrin (VGB) on retinal function and morphology.MethodsTwenty-nine rabbits of mixed strain were divided into two groups, receiving either high-dose (n = 15) or low-dose (n = 14) oral VGB treatment (cumulative dose 29.8 ± 2.9 g and 14.2 ± 0.6 g respectively). Ten rabbits receiving water served as control animals. The rabbits underwent three baseline ff-ERG measurements before initiation of VGB medication and two ff-ERG registrations during treatment, after 8 and 12–14 weeks respectively. At the end of the study, the expression of protein kinase C-alpha (PKC-alpha), gamma amino butyric acid (GABA) A receptors, vimentin, glial fibrillary acidic protein (GFAP) and peanut agglutinin (PNA) was examined in retinal sections from all rabbits.ResultsIn animals of the high-dose group, the ff-ERG measurements revealed a significant decrease of isolated rod b-wave amplitudes, combined rod-cone b-wave amplitudes and amplitudes of oscillatory potentials (OPs); OP1, OP2 and OP3. In the low-dose group, the b-wave amplitudes of combined rod-cone responses as well as OP2 and OP3 were significantly reduced. PKC-alpha labeling demonstrated a dose-related translocation of the enzyme in rod bipolar cells, also revealing a significant decline of the number of PKC-alpha labeled rod bipolar cells in treated animals. Vimentin labeling showed a dose-related deviant labeling pattern of Müller cells, with strikingly low labeling intensity in the outer parts of the cells; in the outer limiting membrane (OLM) as well as the outer nuclear layer (ONL). Labeling with antibodies against GABA A receptors and GFAP, as well as PNA staining, revealed no differences between treated animals and controls.ConclusionsIn this study, VGB medication was associated, in a dose-related manner, with a decrease of ff-ERG amplitudes as well as with altered protein expression in rod bipolar cells and Müller cells, suggesting alterations of inner retinal function. The dose-related morphological and electrophysiological changes indicate a retinal pathology that may explain the constricted visual fields seen in some patients treated with VGB.

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