title: Aberrant mTOR signaling and disrupted autophagy: The missing link in potential vigabatrin-associated ocular toxicity?
abstract: Vigabatrin (VGB; γ-vinylGABA) is a unique antiepileptic directly elevating CNS GABA via inactivation of the GABA metabolic enzyme GABA-transaminase. VGB is effective in treating infantile spasms, a rare seizure disorder associated with significant morbidity. The potential for unexplained bilateral constriction of the visual field associated with VGB intervention can severely limit its temporal utility. Removal of this potential adverse effect with adjuvant intervention(s) would represent a significant advance in epilepsy therapeutics.
authors.affiliation: Division of Experimental and Systems Pharmacology, College of Pharmacy, Washington State University, Spokane, Washington, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Vogel
authors.affiliation: Division of Experimental and Systems Pharmacology, College of Pharmacy, Washington State University, Spokane, Washington, USA.
authors.forename: G R
authors.initials: GR
authors.lastname: Ainslie
authors.affiliation: Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: P L
authors.initials: PL
authors.lastname: Pearl
authors.affiliation: Division of Experimental and Systems Pharmacology, College of Pharmacy, Washington State University, Spokane, Washington, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Gibson
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects*; D001343:Autophagy / Q000187:drug effects*; D005074:Evoked Potentials, Visual; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015398:Signal Transduction; D013036:Spasms, Infantile; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects*; D020888:Vigabatrin / Q000009:adverse effects*; D014786:Vision Disorders / Q000139:chemically induced* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
chemical_list: D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020888:Vigabatrin