Dose-related changes in retinal function and PKC-alpha expression in rabbits on vigabatrin medication : Effect of vigabatrin in the rabbit eye.
(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:
https://lup.lub.lu.se/record/1412744
- author
- Kjellström, Ulrika LU ; Bruun, Anitha LU ; Ghosh, Fredrik LU ; Andréasson, Sten LU and Ponjavic, Vesna LU
- organization
- publishing date
- 2009
- 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
- 2016-04-01 12:38:21
- date last changed
- 2022-01-27 07:50:26
@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}},
doi = {{10.1007/s00417-009-1093-7}},
volume = {{247}},
year = {{2009}},
}