Advanced

Dose-related changes in retinal function and PKC-alpha expression in rabbits on vigabatrin medication : Effect of vigabatrin in the rabbit eye.

Kjellström, Ulrika LU ; Bruun, Anitha LU ; Ghosh, Fredrik LU ; Andréasson, Sten LU and Ponjavic, Vesna LU (2009) In Graefe's Archive for Clinical and Experimental Ophthalmology 247(8). p.1057-1067
Abstract
BACKGROUND: To investigate, in a rabbit model, the effect of two different doses of vigabatrin (VGB) on retinal function and morphology. METHODS: Twenty-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... (More)
BACKGROUND: To investigate, in a rabbit model, the effect of two different doses of vigabatrin (VGB) on retinal function and morphology. METHODS: Twenty-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. RESULTS: In 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. CONCLUSIONS: In 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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Graefe's Archive for Clinical and Experimental Ophthalmology
volume
247
issue
8
pages
1057 - 1067
publisher
Springer
external identifiers
  • wos:000267896700007
  • pmid:19412701
  • scopus:67651097680
ISSN
1435-702X
DOI
10.1007/s00417-009-1093-7
language
English
LU publication?
yes
id
8dbcd382-933d-4ca5-9453-b9238b0812ee (old id 1412744)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19412701?dopt=Abstract
date added to LUP
2009-06-01 10:55:45
date last changed
2017-01-01 05:19:23
@article{8dbcd382-933d-4ca5-9453-b9238b0812ee,
  abstract     = {BACKGROUND: To investigate, in a rabbit model, the effect of two different doses of vigabatrin (VGB) on retinal function and morphology. METHODS: Twenty-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. RESULTS: In 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. CONCLUSIONS: In 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.},
  author       = {Kjellström, Ulrika and Bruun, Anitha and Ghosh, Fredrik and Andréasson, Sten and Ponjavic, Vesna},
  issn         = {1435-702X},
  language     = {eng},
  number       = {8},
  pages        = {1057--1067},
  publisher    = {Springer},
  series       = {Graefe's Archive for Clinical and Experimental Ophthalmology},
  title        = {Dose-related changes in retinal function and PKC-alpha expression in rabbits on vigabatrin medication : Effect of vigabatrin in the rabbit eye.},
  url          = {http://dx.doi.org/10.1007/s00417-009-1093-7},
  volume       = {247},
  year         = {2009},
}