Denervation of the Lacrimal Gland Leads to Corneal Hypoalgesia in a Novel Rat Model of Aqueous Dry Eye Disease
Denervation of the Lacrimal Gland Leads to Corneal Hypoalgesia in a Novel Rat Model of Aqueous Dry Eye Disease
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DOI：
10.1167/iovs.15-17497
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发表时间：
2015-10-01
影响因子：
4.4
通讯作者：
Hegarty, Deborah M.
中科院分区：
文献类型：
--
作者：
Aicher, Sue A.;Hermes, Sam M.;Hegarty, Deborah M.
目的。一些干眼病(DED)患者对角膜刺激有敏感性反应，而另一些患者则经历痛觉减退。许多患者的泪液分泌正常，这表明泪液减少并不总是导致DED感觉功能障碍的原因。在这项研究中，我们表明，泪腺神经支配的中断可以在不改变基础泪液产量的情况下产生痛觉减退。方法：将皂苷毒素结合物注射到雄性SD大鼠的眶外泪腺中，以阻断该腺体的胆碱能神经支配。用酚线试验评估泪液产量。用擦眼行为评估角膜对伤害性刺激的感觉反应。结果：皂苷DED动物泪腺的胆碱能神经支配和乙酰胆碱含量显著减少，而基础泪液生成正常。Saporin DED动物对应用辣椒素的角膜表现出正常的眼部擦拭反应，但对角膜薄荷醇表现出低痛反应。Saporin DED动物角膜神经纤维密度正常。阿托品处理的动物泪液分泌减少，但对眼刺激的反应正常。结论：由于只有薄荷醇反应受损，在我们的Saporin DED模型中，冷敏感的角膜传入似乎有选择性地改变。痛觉减退不是由于泪液分泌减少所致，因为我们没有在阿托品DED模型中观察到痛觉减退。Saporin DED动物的角膜纤维密度没有改变，这表明伤害性信号的分子机制可能受到了损害。Saporin DED模型将有助于探讨角膜低痛觉的机制。
PURPOSE. Some dry eye disease (DED) patients have sensitized responses to corneal stimulation, while others experience hypoalgesia. Many patients have normal tear production, suggesting that reduced tears are not always the cause of DED sensory dysfunction. In this study, we show that disruption of lacrimal innervation can produce hypoalgesia without changing basal tear production.METHODS. Injection of a saporin toxin conjugate into the extraorbital lacrimal gland of male Sprague-Dawley rats was used to disrupt cholinergic innervation to the gland. Tear production was assessed by phenol thread test. Corneal sensory responses to noxious stimuli were assessed using eye wipe behavior. Saporin DED animals were compared to animals treated with atropine to produce aqueous DED.RESULTS. Cholinergic innervation and acetylcholine content of the lacrimal gland were significantly reduced in saporin DED animals, yet basal tear production was normal. Saporin DED animals demonstrated normal eye wipe responses to corneal application of capsaicin, but showed hypoalgesia to corneal menthol. Corneal nerve fiber density was normal in saporin DED animals. Atropine-treated animals had reduced tear production but normal responses to ocular stimuli.CONCLUSIONS. Because only menthol responses were impaired, cold-sensitive corneal afferents appear to be selectively altered in our saporin DED model. Hypoalgesia is not due to reduced tear production, since we did not observe hypoalgesia in an atropine DED model. Corneal fiber density is unaltered in saporin DED animals, suggesting that molecular mechanisms of nociceptive signaling may be impaired. The saporin DED model will be useful for exploring the mechanism underlying corneal hypoalgesia.