Trigeminal-autonomic relations in ocular homeostasis

眼稳态中的三叉神经自主关系

• 批准号: 8130159
• 负责人: DAVID A BEREITER
• 金额: $ 37.17万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8130159
• 关键词: Acids; Affect; Autonomic nervous system; Biological Models; Blood Vessels; Blood flow; Brain; Brain Stem; Caliber; Cell Nucleus; Cervical; Complex; Cornea; Coupled; Couples; Craniofacial Pain; Endothelin; Endothelin A Receptor; Eye; Eye Injuries; Eye diseases; FOS gene; Figs - dietary; Functional disorder; Glaucoma; Goals; Homeostasis; Infection; Lacrimation; Lead; Light; Limb structure; Maintenance; Mass Spectrum Analysis; Mechanics; Mediating; Microinjections; Monitor; Neural Inhibition; Neurons; Nitric Oxide; Nitric Oxide Synthase; Nociception; Nuclear; Ocular Hypertension; Operative Surgical Procedures; Organ; Pain; Parasympathetic Nervous System; Pathway interactions; Peripheral; Photophobia; Physiologic Intraocular Pressure; Process; Property; Proteome; Reflex action; Retina; Role; Sampling; Sensory; Sensory Nerve Endings; Source; Staining method; Stains; Stimulus; Structure; Structure of trigeminal ganglion; Symptoms; Synapses; Testing; Thalamic structure; Tissues; Tracer; Trauma; Trigeminal System; Trigeminal nerve structure; Vision; Visual; Visual Acuity; Visual Pathways; afferent nerve; arm; autonomic reflex; base; brain pathway; design; eye dryness; ganglion cell; indexing; insight; lacrimal; nerve supply; neurophysiology; novel; ocular surface; prevent; receptor; relating to nervous system; research study; response; sensory system; transmission process

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.

描述（由申请人提供）：眼睛的组织经过精心设计，可以保护我们最敏感的终末器官视网膜。对眼睛的环境挑战会引起维持眼部血流、眼内压、瞳孔直径和流泪的多种反射。正常的眼部反射功能依赖于完整的三叉神经感觉系统的充分表达。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。该项目的长期目标是确定三叉神经和 PaNS 通路如何相互作用以介导眼部稳态和反射性流泪。供应眼睛的三叉神经感觉神经终止于下脑干的两个空间不同的区域，即三叉神经极间/尾肌过渡区（Vi/Vc）和三叉神经尾肌/颈索交界处（Vc/C1）区域。尽管人们对角膜感觉神经了解很多，但对供应眼内组织的三叉神经知之甚少。为了帮助这项工作，我们开发了一种使用亮光的新型非侵入性刺激范例。明亮的光线会引起流泪，并选择性地兴奋眼内三叉神经，进而刺激 Vc/C1 交界处的二级神经元。明亮的光诱发的 Vc/C1 神经活动需要在辅助视觉通路中进行中继，增加 PaNS 流向眼睛以及通过三叉神经节的传输。为了更好地了解眼内三叉神经如何促进 PaNS 介导的反射，我们将测试一个总体假设，即眼内和眼表三叉神经投射到两个空间不同的三叉神经脑干区域中的常见二阶神经元，这些神经元服务于眼稳态的不同方面。目标 1 使用单神经元记录和操作改变眼部血流和 PaNS 递质释放，确定眼睛中将亮光与三叉神经脑干活动耦合的外围机制。目标 2 确定 Vi/Vc 过渡区域光响应神经元的属性和传出投射，因为目前仅测试了 Vc/C1 神经元的亮光敏感性。目标 3 确定上唾液核和 Edinger-Westphal 核对强光诱发的三叉神经脑干神经反应的作用，这是影响不同眼组织血流的 PaNS 流出到眼睛的主要来源。监测泪液量和成分作为 PaNS 介导的反射活动的指标。该项目将提供有关三叉神经感觉神经和介导眼保护反射的中枢神经系统机制的新信息。三叉神经-PaNS 关系的破坏可能会导致干眼病、青光眼和高眼压症等多种症状，从而导致视力丧失并引起不适。 公共卫生相关性：创伤、手术或感染后视觉功能的维持需要多种稳态反射的协调努力。确定眼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了解大脑通路如何促进眼稳态。