Rahman Mostafeezur, Shiozaki Kazunari, Okamoto Keiichiro, Thompson Randall, Bereiter David A
Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Moos Tower 18-186, 515 Delaware St. SE, Minneapolis, MN 55455, USA.
Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Moos Tower 18-186, 515 Delaware St. SE, Minneapolis, MN 55455, USA.
Neuroscience. 2017 May 4;349:208-219. doi: 10.1016/j.neuroscience.2017.03.003. Epub 2017 Mar 11.
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 GABA 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 GABA 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.
角膜反射活动改变是干眼病（DE）的一个常见特征。三叉神经感觉神经支配眼表，并在三叉神经极间/尾侧（ViVc）过渡区和脊髓延髓（VcC1）区域终止。虽然这两个区域都参与角膜反射，但它们在干眼条件下的作用尚不清楚。本研究评估了在摘除眶外腺（DE）的乌拉坦麻醉雄性大鼠中，ViVc过渡区和VcC1区域局部抑制性和兴奋性氨基酸神经传递对高渗盐水（HS）诱发的眼轮匝肌活动（OOemg）的影响。与假手术大鼠相比，HS增加了DE大鼠中长时间OOemg活动（OOemgL，>200ms）的幅度，而两组的短时间OOemg活动（OOemgS，<200ms）相似。GABA受体激动剂蝇蕈醇对ViVc过渡区的抑制作用极大地降低了DE大鼠中HS诱发的OOemgL活动，而在VcC1区域注射则对两组的影响较小。在ViVc过渡区或VcC1区域用甲磺酸荷包牡丹碱阻断GABA受体增加了DE大鼠中HS诱发的OOemgL活动。在任一区域阻断N-甲基-D-天冬氨酸（NMDA）受体均可降低DE和假手术大鼠中HS诱发的OOemgL活动。DE大鼠中ViVc过渡区的GABAαβ3受体密度降低，而两个区域的NMDA受体密度均增加。ViVc过渡区GABA能抑制的丧失，加上ViVc过渡区和VcC1区域NMDA兴奋性氨基酸神经传递的增强，可能导致干眼条件下角膜反射的改变。
