Neural mechanisms underlying photophobia and dry eye

畏光和干眼症的神经机制

• 批准号: 9885368
• 负责人: Anat Galor
• 金额: --
• 依托单位: MIAMI VA HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9885368
• 关键词: Ache; Activities of Daily Living; Acute; Address; Affect; Aftercare; Age; Algorithms; Automobile Driving; Bilateral; Botulinum Toxins; Cell Nucleus; Chronic; Computers; Control Groups; Cornea; Cutaneous; Darkness; Data; Diagnosis; Disease; Distress; Dryness; Esthesia; Event; Eye; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Home environment; Image; Individual; Injections; Intrinsic drive; Knowledge; Light; Measures; Medial; Morbidity - disease rate; Nerve; Nerve Block; Neural Pathways; Neuraxis; Neuronal Plasticity; Nociception; Pain; Pain Measurement; Participant; Pathologic; Pathway interactions; Patients; Peripheral; Photophobia; Photosensitivity; Physical Function; Population; Positioning Attribute; Prisoner; Process; Pulvinar structure; Quality of life; Reading; Rehabilitation therapy; Reporting; Retinal Ganglion Cells; Scanning; Severities; Signal Transduction; Signs and Symptoms; Somatosensory Cortex; Stimulus; Structure of trigeminal ganglion; Symptoms; Syndrome; System; Technology; Testing; Thalamic structure; Therapeutic; Trigeminal Nuclei; Trigeminal System; Veterans; Vision; Work; blood oxygen level dependent; botulinum; clinical pain; design; effective therapy; experience; eye dryness; improved; individual patient; instrument; melanopsin; mental function; multidisciplinary; neuromechanism; ocular pain; pain sensation; pain symptom; painful neuropathy; patient subsets; precision medicine; programs; relating to nervous system; response; sex; social; statistics; sunglasses; targeted treatment; tool; treatment response; treatment strategy

It is estimated that 19% of US veterans have dry eye (DE), of which painful ocular symptoms are a common manifestation. These can include sensations of dryness, burning, and extreme sensitivity to light (i.e., photophobia). The symptoms interfere with activities of daily living including driving and reading. Photophobia, in particular, is one of the most distressing symptoms as its occurrence results in high morbidity without effective treatment. Individuals most severely affected become prisoners in their own homes due to intolerance to even small amounts of light. Even in less severe cases, most individuals have significant functional limitations and often require sunglasses in and outdoors. A knowledge gap exists with regards to the mechanism that underlie these painful sensations, thus limiting the ability to target appropriate treatment strategies. Our overall hypothesis is that photophobia is an indicator of central pathologic plasticity of 1) trigeminal pathways, and 2) their interaction with melanopsin pathways. To test this hypothesis, in aim 1, we define peripheral and central neural responses to light in individuals with chronic ocular pain and photophobia as compared to controls. In aim 2, we examine the contribution of different pathways to photophobia by blocking corneal afferent drive (to assess trigeminal pathways) and intrinsically photosensitive retinal ganglion cell (ipRGC) drive (to assess melanopsin pathways). In Aim 3, we determine the effect of neural blockade with botulinum toxin injection on photophobia. This study is greatly needed, as a critical barrier to progress in the field is the lack of information on neural pathways that underlie disease. The data generated can be used to improve the rehabilitation of ocular pain and increase function and quality of life in veterans and non-veterans alike.

据估计，19% 的美国退伍军人患有干眼症 (DE)，其中眼部疼痛症状是常见的症状 表现。这些可能包括干燥、灼烧感和对光极度敏感的感觉（即， 畏光）。这些症状会干扰日常生活活动，包括驾驶和阅读。畏光， 特别是，它是最令人痛苦的症状之一，因为如果没有有效的治疗，它的发生会导致高发病率 治疗。受影响最严重的个人由于不容忍甚至成为自己家中的囚犯 少量的光。即使在不太严重的情况下，大多数人也有明显的功能限制 在室内外经常需要佩戴太阳镜。关于其背后的机制存在知识差距 这些痛苦的感觉，从而限制了制定适当治疗策略的能力。我们的总体假设 畏光是 1）三叉神经通路和 2）它们相互作用的中心病理可塑性的一个指标 与黑视蛋白途径。为了检验这一假设，在目标 1 中，我们定义了外周和中枢神经反应 与对照组相比，患有慢性眼痛和畏光的个体接受光照。在目标 2 中，我们检查 通过阻断角膜传入驱动不同途径对畏光的贡献（以评估三叉神经 通路）和本质光敏视网膜神经节细胞（ipRGC）驱动（以评估黑视蛋白通路）。 在目标 3 中，我们确定了肉毒毒素注射神经阻断对畏光的影响。这项研究是 非常需要，因为缺乏有关神经通路的信息是该领域取得进展的一个关键障碍 是疾病的根源。生成的数据可用于改善眼部疼痛的康复并增加 退伍军人和非退伍军人的功能和生活质量。