Neural mechanisms underlying photophobia and dry eye

据估计，19%的美国退伍军人患有干眼（DE），其中疼痛的眼部症状是常见的 表现。这些可能包括干燥、灼热和对光极度敏感的感觉（即， 恐惧症）。症状干扰日常生活活动，包括驾驶和阅读。畏光症， 特别是，它是最令人痛苦的症状之一，因为它的发生导致高发病率， 治疗受影响最严重的人甚至由于对人权的不容忍而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， 在室内和室外经常需要太阳镜。关于其背后的机制存在知识差距， 这些疼痛的感觉，从而限制了针对适当的治疗策略的能力。我们的总体假设 恐惧症是1）三叉神经通路和2）它们之间相互作用的中枢病理可塑性的指标 与黑视蛋白通路有关。为了验证这一假设，在aim 1中，我们定义了外周和中枢神经反应 与对照组相比，慢性眼痛和眼恐怖症患者的视力下降。在目标2中，我们检查 通过阻断角膜传入驱动（以评估三叉神经 通路）和内在光敏视网膜神经节细胞（ipRGC）驱动（以评估黑视素通路）。 在目的3中，我们确定肉毒杆菌毒素注射神经阻滞对恐惧症的影响。本研究 非常需要，因为该领域进展的关键障碍是缺乏关于神经通路的信息， 潜在的疾病所产生的数据可用于改善眼部疼痛的康复，并增加 功能和生活质量的退伍军人和非退伍军人一样。

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.