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    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 GABAA receptor 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 GABAA receptors 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. Published by Elsevier Ltd.

    Citation

    Mostafeezur Rahman, Kazunari Shiozaki, Keiichiro Okamoto, Randall Thompson, David A Bereiter. Trigeminal brainstem modulation of persistent orbicularis oculi muscle activity in a rat model of dry eye. Neuroscience. 2017 May 04;349:208-219


    PMID: 28288901

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