Trigeminal-autonomic relations in ocular homeostasis

眼稳态中的三叉神经自主关系

• 批准号: 8240030
• 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/8240030
• 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; Public Health; 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. 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）：眼睛的组织旨在保护我们最敏感的末端器官视网膜。对眼睛的环境挑战引起了维持眼部血流，眼内压，瞳孔直径和泪液的多种反射。正常的眼反射函数取决于完整的三叉气感觉系统的完整表达。三叉神经几乎可以提供眼睛的所有组织，并充当许多由副交感神经系统（PAN）介导的许多保护性反射的传入肢体。该项目的长期目标是确定三叉神经和平底锅途径如何相互作用，以介导眼稳态和反射富富。供应眼睛的三叉神经感官在下部脑干的两个空间不同区域，三叉神经际/尾caudalis跃迁（VI/VC）和三叉神经caudalis/宫颈索连接（VC/C1）区域。尽管对角膜感觉神经知之甚少，但对供应人眼组织的三叉神经知之甚少。为了帮助这项工作，我们开发了一种新型的非侵入性刺激范式，该范式使用明亮的光。明亮的光引起泪液并有选择性激发的眼内三叉神经，进而在VC/C1连接处进行二阶神经元。明亮的光诱发的VC/C1神经活动需要在附件视觉途径中进行继电器，增加了眼睛向眼睛流出并通过三叉神经节传播。为了更好地了解眼内三叉神经如何有助于PANS介导的反射，我们将检验以下总体假设，即在两个空间不同的三叉神经脑干区域中，眼内和眼内表面三叉神经投射到公共二阶神经元，这些神经元有效地服务于Ocular稳态的不同方面。 AIM 1确定了眼睛的外围机制，即使用单个神经元记录和操纵改变眼部血流和PANS发射器释放的单个神经元记录和操纵。 AIM 2确定了VI/VC过渡区域的光响应神经元的特性和传出投影，因为目前仅测试了VC/C1神经元的光敏感性。 AIM 3确定了上唾液和埃丁 - 韦斯特法核在明亮的光诱发三叉神经神经反应上的作用，这是影响血液流向不同眼组织的血液流向眼睛的主要来源。撕裂体积和成分被监测为PANS介导的反射活性的指数。该项目将提供有关介导眼部保护反射的三叉神经和中枢神经系统机制的作用的新信息。三叉神经关系的破坏可能会导致在干眼症，青光眼和眼部高血压的各种疾病中的症状，从而导致视力丧失并引起不适感。 公共卫生相关性：创伤，手术或感染后视觉功能的维持需要几种体内反射的协调努力。确定三叉神经在眼部损伤后如何与自主神经系统相互作用可能有助于了解脑途径如何对眼部稳态有效。