Vigabatrin-induced retinal toxicity is partially mediated by signaling in rod and cone photoreceptors.

Vigabatrin (VGB) is a commonly prescribed antiepileptic drug designed to inhibit GABA-transaminase, effectively halting seizures. Unfortunately, VGB treatment is also associated with the highest frequencies of peripheral visual field constriction of any of the antiepileptic drugs and the mechanisms...

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Autori principali: Jin Yang, Matthew C Naumann, Yi-Ting Tsai, Joaquin Tosi, Deniz Erol, Chyuan-Sheng Lin, Richard J Davis, Stephen H Tsang
Natura: Articolo
Lingua:English
Pubblicazione: Public Library of Science (PLoS) 2012-01-01
Serie:PLoS ONE
Accesso online:http://europepmc.org/articles/PMC3431405?pdf=render
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author Jin Yang
Matthew C Naumann
Yi-Ting Tsai
Joaquin Tosi
Deniz Erol
Chyuan-Sheng Lin
Richard J Davis
Stephen H Tsang
author_facet Jin Yang
Matthew C Naumann
Yi-Ting Tsai
Joaquin Tosi
Deniz Erol
Chyuan-Sheng Lin
Richard J Davis
Stephen H Tsang
author_sort Jin Yang
collection DOAJ
description Vigabatrin (VGB) is a commonly prescribed antiepileptic drug designed to inhibit GABA-transaminase, effectively halting seizures. Unfortunately, VGB treatment is also associated with the highest frequencies of peripheral visual field constriction of any of the antiepileptic drugs and the mechanisms that lead to these visual field defects are uncertain. Recent studies have demonstrated light exposure exacerbates vigabatrin-induced retinal toxicity. We further assessed this relationship by examining the effects of vigabatrin treatment on the retinal structures of mice with genetically altered photoreception. In keeping with previous studies, we detected increased toxicity in mice exposed to continuous light. To study whether cone or rod photoreceptor function was involved in the pathway to toxicity, we tested mice with mutations in the cone-specific Gnat2 or rod-specific Pde6g genes, and found the mutations significantly reduced VGB toxicity. Our results confirm light is a significant enhancer of vigabatrin toxicity and that a portion of this is mediated, directly or indirectly, by phototransduction signaling in rod and cone photoreceptors.
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spelling doaj.art-4f156943f4d74f4d91d69ce3c96ccbd02022-12-21T23:23:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4388910.1371/journal.pone.0043889Vigabatrin-induced retinal toxicity is partially mediated by signaling in rod and cone photoreceptors.Jin YangMatthew C NaumannYi-Ting TsaiJoaquin TosiDeniz ErolChyuan-Sheng LinRichard J DavisStephen H TsangVigabatrin (VGB) is a commonly prescribed antiepileptic drug designed to inhibit GABA-transaminase, effectively halting seizures. Unfortunately, VGB treatment is also associated with the highest frequencies of peripheral visual field constriction of any of the antiepileptic drugs and the mechanisms that lead to these visual field defects are uncertain. Recent studies have demonstrated light exposure exacerbates vigabatrin-induced retinal toxicity. We further assessed this relationship by examining the effects of vigabatrin treatment on the retinal structures of mice with genetically altered photoreception. In keeping with previous studies, we detected increased toxicity in mice exposed to continuous light. To study whether cone or rod photoreceptor function was involved in the pathway to toxicity, we tested mice with mutations in the cone-specific Gnat2 or rod-specific Pde6g genes, and found the mutations significantly reduced VGB toxicity. Our results confirm light is a significant enhancer of vigabatrin toxicity and that a portion of this is mediated, directly or indirectly, by phototransduction signaling in rod and cone photoreceptors.http://europepmc.org/articles/PMC3431405?pdf=render
spellingShingle Jin Yang
Matthew C Naumann
Yi-Ting Tsai
Joaquin Tosi
Deniz Erol
Chyuan-Sheng Lin
Richard J Davis
Stephen H Tsang
Vigabatrin-induced retinal toxicity is partially mediated by signaling in rod and cone photoreceptors.
PLoS ONE
title Vigabatrin-induced retinal toxicity is partially mediated by signaling in rod and cone photoreceptors.
title_full Vigabatrin-induced retinal toxicity is partially mediated by signaling in rod and cone photoreceptors.
title_fullStr Vigabatrin-induced retinal toxicity is partially mediated by signaling in rod and cone photoreceptors.
title_full_unstemmed Vigabatrin-induced retinal toxicity is partially mediated by signaling in rod and cone photoreceptors.
title_short Vigabatrin-induced retinal toxicity is partially mediated by signaling in rod and cone photoreceptors.
title_sort vigabatrin induced retinal toxicity is partially mediated by signaling in rod and cone photoreceptors
url http://europepmc.org/articles/PMC3431405?pdf=render
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