TRPV1 and TRPM8 Channels and Nocifensive Behavior in a Rat Model for Dry Eye.
TRPV1 and TRPM8 Channels and Nocifensive Behavior in a Rat Model for Dry Eye.
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DOI：
10.1167/iovs.18-24304
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发表时间：
2018-07-02
影响因子：
4.4
通讯作者：
Saito H
中科院分区：
文献类型：
--
作者：
Bereiter DA;Rahman M;Thompson R;Stephenson P;Saito H
持续性眼表疼痛发生在中度至重度干眼症（DE）;然而，这种症状的机制仍然不确定。本研究的目的是确定瞬时受体电位香草酸离子通道是否在高渗盐水（HS）诱发的角膜反射中发挥作用，在水泪液缺乏DE模型。在摘除眶外腺后14天，在眼部滴注HS、辣椒素或薄荷醇后测量擦眼行为和眼轮匝肌活动（OOemg）。取Sham组和DE组大鼠眼前节和三叉神经节组织，测定总RNA和蛋白质含量。与假手术大鼠相比，HS和辣椒素滴注后DE大鼠的擦眼行为增强，但薄荷醇后没有增强。DE大鼠表现出更大的OOemg活动后HS和辣椒素，但不是薄荷醇后，与假手术大鼠相比。选择性TRPV 1拮抗剂和辣椒素加QX-314（一种带电的利多卡因衍生物）的共同应用可降低HS诱发的OOemg活性。Menglutamine不影响OOemg活性;然而，TRPM 8的选择性拮抗作用降低了HS诱发的OOemg活性。TRPV 1蛋白水平在DE大鼠的眼前节和三叉神经节样品中增加，而TRPM 8水平不受影响。这些结果表明TRPV 1在DE中介导增强的伤害性行为中起重要作用，而TRPM 8可能起较小的作用。靶向角膜神经上的特定换能器分子的策略可能被证明是有益的，作为管理中度至重度DE病例的眼部疼痛的辅助疗法。
Persistent ocular surface pain occurs in moderate to severe dry eye disease (DE); however, the mechanisms that underlie this symptom remain uncertain. The aim of this study was to determine if the transient receptor potential vanilloid ion channels play a role in hypertonic saline (HS)-evoked corneal reflexes in a model for aqueous tear deficient DE. Eye wipe behavior and orbicularis oculi muscle activity (OOemg) were measured after ocular instillation of HS, capsaicin, or menthol 14 days after exorbital gland removal. Total RNA and protein were measured from anterior eye segment and trigeminal ganglia of sham and DE rats. Eye wipe behavior was enhanced in DE rats after HS and capsaicin instillation, but not after menthol when compared to sham rats. DE rats displayed greater OOemg activity after HS and capsaicin, but not after menthol, compared to sham rats. HS-evoked OOemg activity was reduced by selective TRPV1 antagonists and by coapplication of capsaicin plus QX-314, a charged lidocaine derivative. Menthol did not affect OOemg activity; however, selective antagonism of TRPM8 reduced HS-evoked OOemg activity. TRPV1 protein levels were increased in anterior eye segment and trigeminal ganglion samples from DE rats, whereas TRPM8 levels were not affected. These results suggest that TRPV1 plays a significant role in mediating enhanced nocifensive behavior in DE, while TRPM8 may play a lesser role. Strategies to target specific transducer molecules on corneal nerves may prove beneficial as adjunct therapies in managing ocular pain in moderate to severe cases of DE.
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影响因子：
5.5
作者：
BELMONTE, C;GALLAR, J;REBOLLO, I
通讯作者：
REBOLLO, I
影响因子：
4.4
作者：
Gonzalez-Gonzalez, Omar;Bech, Federico;Belmonte, Carlos
通讯作者：
Belmonte, Carlos
影响因子：
3.4
作者：
CHEN, XJ;GALLAR, J;BELMONTE, C
通讯作者：
BELMONTE, C
影响因子：
2
作者：
MANNING, KA;EVINGER, C
通讯作者：
EVINGER, C
影响因子：
7.4
作者：
Chen, XJ;Belmonte, C;Rang, HP
通讯作者：
Rang, HP