ArticlePediatric neurology2017
mTOR Inhibition Mitigates Molecular and Biochemical Alterations of Vigabatrin-Induced Visual Field Toxicity in Mice.
Article in Pediatric neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The trial behind it
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Testing for pharmacogenomic predictors of ppRNFL thinning in individuals exposed to vigabatrin.Frontiers in neuroscience · 2023Article
- Use of Visual Electrophysiology to Monitor Retinal and Optic Nerve Toxicity.Biomolecules · 2022Review
- The Ameliorative Effect of Empagliflozin in Vigabatrin-Induced Cerebellar/Neurobehavioral Deficits: Targeting mTOR/AMPK/SIRT-1 Signaling Pathways.Molecules (Basel, Switzerland) · 2022Article
- Vigabatrin-associated brain abnormalities on MRI in tuberous sclerosis complex patients with infantile spasms: are they preventable?Therapeutic advances in neurological disorders · 2022Article
- Modulation of vigabatrin induced cerebellar injury: the role of caspase-3 and RIPK1/RIPK3-regulated cell death pathways.Journal of molecular histology · 2021Article
- Transcriptome analysis in mice treated with vigabatrin identifies dysregulation of genes associated with retinal signaling circuitry.Epilepsy research · 2020Article
- Metabolomic analyses of vigabatrin (VGB)-treated mice: GABA-transaminase inhibition significantly alters amino acid profiles in murine neural and non-neural tissues.Neurochemistry international · 2019Article
- Preclinical tissue distribution and metabolic correlations of vigabatrin, an antiepileptic drug associated with potential use-limiting visual field defects.Pharmacology research & perspectives · 2019Article
- Succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism: an update on pharmacological and enzyme-replacement therapeutic strategies.Journal of inherited metabolic disease · 2018Review
- Toxicologic/transport properties of NCS-382, a γ-hydroxybutyrate (GHB) receptor ligand, in neuronal and epithelial cells: Therapeutic implications for SSADH deficiency, a GABA metabolic disorder.Toxicology in vitro : an international journal published in association with BIBRA · 2018Article
- Aberrant mTOR signaling and disrupted autophagy: The missing link in potential vigabatrin-associated ocular toxicity?Clinical pharmacology and therapeutics · 2017Article
- In vitro modeling of experimental succinic semialdehyde dehydrogenase deficiency (SSADHD) using brain-derived neural stem cells.PloS one · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGamma-vinyl-γ-aminobutyric acid (GABA) (vigabatrin) is an antiepileptic drug and irreversible GABA transaminase inhibitor associated with visual field impairment, which limits its clinical utility. We sought to relate altered visual evoked potentials associated with vigabatrin intake to transcriptional changes in the mechanistic target of rapamycin (mTOR) pathway and GABA receptors to expose further mechanisms of vigabatrin-induced visual field loss.
methodsVigabatrin was administered to mice via an osmotic pump for two weeks to increase GABA levels. Visual evoked potentials were examined, eye samples were collected, and gene expression was measured by quantitative reverse transcription-polymerase chain reaction. Similarly, human retinal pigment epithelial cells (ARPE19) were exposed to vigabatrin and treated with mTOR inhibitors for mTOR pathway analysis and to assess alterations in organelle accumulation by microscopy.
resultsDysregulated expression of transcripts in the mTOR pathway, GABA
conclusionsOur studies, indicating GABA-associated augmentation of RRAG and mTOR signaling, support further preclinical evaluation of mTOR inhibitors as a therapeutic strategy to potentially mitigate vigabatrin-induced ocular toxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.