Trigeminal-autonomic relations in ocular homeostasis

眼稳态中的三叉神经自主关系

• 批准号: 8461195
• 负责人: DAVID A BEREITER
• 金额: $ 35.31万
• 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 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8461195
• 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; Trigeminal subnucleus caudalis; 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; public health relevance; 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.

描述（申请人提供）：眼睛的组织设计良好，以保护视网膜，我们最敏感的末端器官。环境对眼睛的挑战引起了维持眼血流、眼内压、瞳孔直径和流泪的各种反射。正常的眼反射功能依赖于三叉神经感觉系统的完整表达。三叉神经几乎供应眼睛的所有组织，并作为传入肢体，由副交感神经系统（PaNS）介导的许多保护性反射。该项目的长期目标是确定三叉神经通路和pan通路如何相互作用以介导眼内稳态和反射性流泪。供应眼睛的三叉感觉神经在空间上分别终止于脑干下部的两个不同区域：三叉内插/尾侧过渡区（Vi/Vc）和三叉尾侧/颈脊髓交界处（Vc/C1）。虽然我们对角膜感觉神经了解甚多，但对供应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型非侵入性刺激模式。明亮的光线引起流泪，选择性地刺激眼内三叉神经，进而刺激Vc/C1交界处的二级神经元。明亮光诱发的Vc/C1神经活动需要在副视觉通路中进行中继，增加pan向眼睛的流出并通过三叉神经节传递。为了更好地理解眼内三叉神经如何参与泛肽介导的反射，我们将验证一个总体假设，即眼内三叉神经和眼表三叉神经投射到两个空间上不同的三叉脑干区域的共同二级神经元，这些区域在眼内稳态的不同方面起作用。目的1通过单神经元记录和操作来改变眼血流量和pan递质释放，确定眼睛中将明亮光线与三叉脑干活动耦合的外周机制。Aim 2确定了Vi/Vc过渡区的光响应神经元的特性和传出投射，因为目前只有Vc/C1神经元被测试了对明亮光的敏感性。目的3确定上涎核和Edinger-Westphal核在明亮光诱发的三叉脑干神经反应中的作用，三叉脑干神经反应是pan向眼流出的主要来源，影响眼部不同组织的血流量。泪液体积和成分被监测为pan介导的反射活动的一个指标。本项目将为三叉感觉神经的作用和中枢神经系统介导眼保护性反射的机制提供新的信息。三叉神经- pan关系的破坏可能导致干眼病、青光眼和高眼压等多种症状，这些症状可导致视力丧失并引起不适。