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，有19％的美国退伍军人患有干眼症（DE），其中疼痛的眼症状很常见 表现。这些可以包括干燥的感觉，燃烧和对光的极端敏感性（即 畏光）。症状干扰日常生活的活动，包括驾驶和阅读。畏光， 特别是，这是最令人痛苦的症状之一，因为它的发生导致高发病率无效 治疗。由于不容忍甚至 少量的光。即使在不太严重的情况下，大多数人都有明显的功能限制，并且 通常需要在户外和户外太阳镜。知识差距存在于基于的机制 这些痛苦的感觉，因此限制了针对适当治疗策略的能力。我们的总体假设 是恐惧症是1）三叉神经途径的中心病理可塑性的指标，以及2）它们的相互作用 与黑素蛋白途径。为了检验这一假设，在AIM 1中，我们定义了外围和中央神经反应 与对照组相比，患有慢性眼痛和恐惧恐惧症的个体中要发光。在AIM 2中，我们检查 通过阻止角膜传入驱动的不同途径对恐惧恐惧症的贡献（评估三叉状 途径）和内在光敏性的视网膜神经节细胞（IPRGC）驱动器（评估黑素蛋白途径）。 在AIM 3中，我们确定了肉毒杆菌毒素注射对恐惧症的神经阻滞作用。这项研究是 非常需要，作为该领域进步的关键障碍是缺乏有关神经途径的信息 基础疾病。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职能和生活质量。