title: Trigeminal brainstem modulation of persistent orbicularis oculi muscle activity in a rat model of dry eye.
abstract: Altered corneal reflex activity is a common feature of dry eye disease (DE). Trigeminal sensory nerves supply the ocular surface and terminate at the trigeminal interpolaris/caudalis (ViVc) transition and spinomedullary (VcC1) regions. Although both regions contribute to corneal reflexes, their role under dry eye conditions is not well defined. This study assessed the influence of local inhibitory and excitatory amino acid neurotransmission at the ViVc transition and VcC1 regions on hypertonic saline (HS) evoked orbicularis oculi muscle activity (OOemg) in urethane-anesthetized male rats after exorbital gland removal (DE). HS increased the magnitude of long-duration OOemg activity (OOemgL, >200ms) in DE compared to sham rats, while short-duration OOemg activity (OOemgS, <200ms) was similar for both groups. Inhibition of the ViVc transition by muscimol, a GABAAreceptor agonist, greatly reduced HS-evoked OOemgL activity in DE rats, whereas injections at the VcC1 region had only minor effects in both groups. Blockade of GABAAreceptors by bicuculline methiodide at the ViVc transition or VcC1 region increased HS-evoked OOemgL activity in DE rats. Blockade of N-methyl-D-aspartate (NMDA) receptors at either region reduced HS-evoked OOemgL activity in DE and sham rats. GABAαβ3 receptor density was reduced at the ViVc transition, while NMDA receptor density was increased at both regions in DE rats. Loss of GABAergic inhibition at the ViVc transition coupled with enhanced NMDA excitatory amino acid neurotransmission at the ViVc transition and the VcC1 region likely contribute to altered corneal reflexes under dry eye conditions.
authors.affiliation: Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Moos Tower 18-186, 515 Delaware St. SE, Minneapolis, MN 55455, USA. Electronic address: mrahman@umn.edu.
authors.forename: Mostafeezur
authors.initials: M
authors.lastname: Rahman
authors.affiliation: Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Moos Tower 18-186, 515 Delaware St. SE, Minneapolis, MN 55455, USA.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Shiozaki
authors.affiliation: Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Moos Tower 18-186, 515 Delaware St. SE, Minneapolis, MN 55455, USA.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Moos Tower 18-186, 515 Delaware St. SE, Minneapolis, MN 55455, USA.
authors.forename: Randall
authors.initials: R
authors.lastname: Thompson
authors.affiliation: Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Moos Tower 18-186, 515 Delaware St. SE, Minneapolis, MN 55455, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Bereiter
mesh_terms: D000818:Animals; D001767:Blinking / Q000187:drug effects / Q000502:physiology; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D014276:Trigeminal Nerve / Q000187:drug effects / Q000502:physiology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D012462:Saline Solution, Hypertonic; D016202:N-Methylaspartate
keywords: GABA receptor; NMDA receptor; corneal reflex; dry eye; electromyography; orbicularis oculi