Transcriptome analysis in mice treated with vigabatrin identifies dysregulation of genes associated with retinal signaling circuitry.
Epilepsy Res
; 166: 106395, 2020 10.
Article
en En
| MEDLINE
| ID: mdl-32679486
ABSTRACT
Vigabatrin (VGB; γ-vinyl-GABA) is an antiepileptic drug that elevates CNS GABA via irreversible inactivation of the GABA catabolic enzyme GABA-transaminase. VGB's clinical utility, however, can be curtailed by peripheral visual field constriction (pVFC) and thinning of the retinal nerve fiber layer (RNFL). Earlier studies from our laboratory revealed disruptions of autophagy by VGB. Here, we tested the hypothesis that VGB administration to animals would reveal alterations of gene expression in VGB-treated retina that associated with autophagy. VGB (140 mg/kg/d; subcutaneous minipump) was continuously administered to mice (n = 6 each VGB/vehicle) for 12 days, after which animals were euthanized. Retina was isolated for transcriptome (RNAseq) analysis and further validation using qRT-PCR and immunohistochemistry (IHC). For 112 differentially expressed retinal genes (RNAseq), two databases (Gene Ontology; Kyoto Encyclopedia of Genes and Genomes) were used to identify genes associated with visual function. Twenty four genes were subjected to qRT-PCR validation, and five (Gb5, Bdnf, Cplx9, Crh, Sox9) revealed significant dysregulation. IHC of fixed retinas verified significant down-regulation of Gb5 in photoreceptor cells. All of these genes have been previously shown to play a role in retinal function/circuitry signaling. Minimal impact of VGB on retinal autophagic gene expression was observed. This is the first transcriptome analysis of retinal gene expression associated with VGB intake, highlighting potential novel molecular targets potentially related to VGB's well known ocular toxicity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Retina
/
Vías Visuales
/
Vigabatrin
/
Perfilación de la Expresión Génica
/
Anticonvulsivantes
/
Red Nerviosa
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Epilepsy Res
Asunto de la revista:
CEREBRO
/
NEUROLOGIA
Año:
2020
Tipo del documento:
Article