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

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Kjellström, UlrikaLund University,Lunds universitet,Oftalmologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Ophthalmology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine (författare)

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

Artikel/kapitelEngelska2009

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2009-05-03
Springer Science and Business Media LLC,2009

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LIBRIS-ID:oai:lup.lub.lu.se:8dbcd382-933d-4ca5-9453-b9238b0812ee
https://lup.lub.lu.se/record/1412744URI
https://doi.org/10.1007/s00417-009-1093-7DOI

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Språk:engelska
Sammanfattning på:engelska

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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.

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Bruun, AnithaLund University,Lunds universitet,Oftalmologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Ophthalmology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)oft-abr (författare)
Ghosh, FredrikLund University,Lunds universitet,Oftalmologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Ophthalmology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)oft-fgh (författare)
Andréasson, StenLund University,Lunds universitet,Oftalmologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Ophthalmology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)oft-san (författare)
Ponjavic, VesnaLund University,Lunds universitet,Oftalmologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Ophthalmology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)oft-vpo (författare)
Oftalmologi, LundSektion IV (creator_code:org_t)

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Ingår i:Graefe's Archive for Clinical and Experimental Ophthalmology: Springer Science and Business Media LLC247:8, s. 1057-10671435-702X0721-832X

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Av författaren/redakt...: Kjellström, Ulri ...; Bruun, Anitha; Ghosh, Fredrik; Andréasson, Sten; Ponjavic, Vesna

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Oftalmologi

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