Trigeminal-autonomic relations in ocular homeostasis

描述(由申请人提供)：眼睛的组织设计得很好，以保护视网膜，我们最敏感的末端器官。环境对眼睛的挑战唤起了不同的反射，以维持眼睛的血流量、眼压、瞳孔直径和泪水。正常的眼反射功能依赖于完整的三叉神经感觉系统来充分表达。三叉神经几乎供应眼睛的所有组织，并作为副交感神经系统(PANS)介导的许多保护性反射的传入肢体。这个项目的长期目标是确定三叉神经和PAN通路如何相互作用来调节眼睛的动态平衡和反射性泪水。供应眼睛的三叉神经感觉神经终止于下脑干的两个空间上不同的区域，即三叉神经尾侧/尾侧交界区(Vi/Vc)和三叉神经尾侧/颈髓交界区(Vc/C1)。虽然人们对角膜感觉神经了解很多，但对眼内组织的三叉神经知之甚少。为了帮助这一努力，我们开发了一种使用强光的新的非侵入性刺激范例。强光导致眼球内三叉神经撕裂，并选择性地兴奋三叉神经，进而刺激VC/C1交界处的二级神经元。强光诱发的VC/C1神经活动需要在副视觉通路上传递，增加PAN流出到眼睛并通过三叉神经节传递。为了更好地了解眼内三叉神经如何参与PAN介导的反射，我们将检验最重要的假设，即眼内和眼表面三叉神经投射到两个空间上不同的三叉神经脑干区的共同二级神经元，这两个区域服务于眼睛内稳态的不同方面。目的1利用单个神经元记录和改变眼血流和PAN递质释放的手法，确定眼睛中将明亮的光耦合到三叉神经脑干活动的外周机制(S)。目的2确定光反应神经元在Vi/Vc过渡区的性质和传出投射，因为目前只测试Vc/C1神经元对强光的敏感性。目的3确定上唾液核和Edinger-Westphal核团在强光诱发的三叉神经脑干反应中的作用，这是PAN流出到眼睛的主要来源，影响血液流向不同的眼组织。泪液的体积和成分被监测为PAN介导的反射活动的一个指标。这个项目将提供关于三叉神经感觉神经和中枢神经系统机制的新信息，这些机制介导眼睛保护反射。三叉神经-PAN关系的中断可能导致各种情况下的症状，如干眼病、青光眼和高眼压，这些症状可能导致视力丧失和不适。 公共卫生相关性：在创伤、手术或感染后维持视觉功能需要几种平衡反射的协调作用。确定眼睛损伤后三叉神经如何与自主神经系统相互作用，可能有助于理解大脑通路如何促进眼睛内环境平衡。

DESCRIPTION (provided by applicant): The organization of the eye is well designed to protect the retina, our most sensitive end organ. Environmental challenges to the eye evoke diverse reflexes that maintain ocular blood flow, intraocular pressure, pupillary diameter and lacrimation. Normal ocular reflex function depends on an intact trigeminal sensory system for full expression. Trigeminal nerves supply virtually all tissues of the eye and serve as the afferent limb for many protective reflexes mediated by the parasympathetic nervous system (PaNS). The long-term goal of this project is to determine how trigeminal and PaNS pathways interact to mediate ocular homeostasis and reflex lacrimation. Trigeminal sensory nerves that supply the eye terminate in two spatially distinct regions of the lower brainstem, trigeminal interpolaris/caudalis transition (Vi/Vc) and trigeminal caudalis/cervical cord junction (Vc/C1) regions. Although much is known about corneal sensory nerves, little is known about trigeminal nerves that supply intraocular tissues. To aid this effort, we developed a novel non-invasive stimulus paradigm that uses bright light. Bright light caused lacrimation and selectively excited intraocular trigeminal nerves and, in turn, second-order neurons at the Vc/C1 junction. Bright light-evoked Vc/C1 neural activity required a relay in accessory visual pathways, increased PaNS outflow to the eye and transmission through the trigeminal ganglion. To better understand how intraocular trigeminal nerves contribute to PaNS-mediated reflexes we will test the overarching hypothesis that intraocular and ocular surface trigeminal nerves project to common second-order neurons in two spatially distinct trigeminal brainstem regions that serve different aspects of ocular homeostasis. Aim 1 determines the peripheral mechanism(s) in the eye that couples bright light to trigeminal brainstem activity using single neuron recording and manipulations that alter ocular blood flow and PaNS transmitter release. Aim 2 determines the properties and efferent projections of light-responsive neurons at the Vi/Vc transition region, since currently only Vc/C1 neurons have been tested for bright light sensitivity. Aim 3 determines the roles of the superior salivatory and Edinger-Westphal nuclei on bright light-evoked trigeminal brainstem neural responses, the main sources of PaNS outflow to the eye that affect blood flow to different ocular tissues. Tear volume and composition is monitored as an index of PaNS-mediated reflex activity. This project will provide new information on the role of trigeminal sensory nerves and CNS mechanisms that mediate ocular protective reflexes. Disruption of trigeminal-PaNS relations may contribute to symptoms in diverse conditions as dry eye disease, glaucoma and ocular hypertension that can lead to loss of visual acuity and cause discomfort. PUBLIC HEALTH RELEVANCE: Maintenance of visual function after trauma, surgery or infection requires the coordinated effort of several homeostatic reflexes. Determining how the trigeminal nerve interacts with the autonomic nervous system after ocular injury may help understand how brain pathways contribute to ocular homeostasis.