Neural mechanisms underlying photophobia and dry eye

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 显化。这些症状可能包括干燥感、灼热感和对光的极度敏感(即， 恐光症)。这些症状干扰了日常生活活动，包括驾驶和阅读。恐光症， 尤其是最令人痛苦的症状之一，因为它的发生导致了高发病率而没有有效的 治疗。受影响最严重的个人成为自己家中的囚犯，因为即使 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和 经常需要在室内和室外佩戴太阳镜。关于作为基础的机制存在着知识鸿沟 这些痛苦的感觉，从而限制了针对适当的治疗策略的能力。我们的总体假设 恐光是1)三叉神经通路和2)三叉神经通路相互作用的中枢病理可塑性的指标 通过黑素途径。为了验证这一假设，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，慢性眼痛和畏光患者的光线。在目标2中，我们检查 通过阻断角膜传入驱动(评估三叉神经)不同通路在畏光中的作用 和固有的光敏视网膜神经节细胞(IpRGC)驱动(以评估黑素途径)。 在目的3中，我们确定了神经阻滞联合肉毒杆菌毒素注射治疗畏光的效果。这项研究是 作为该领域取得进展的一个关键障碍，迫切需要的是缺乏关于神经通路的信息 潜伏的疾病。所产生的数据可以用于改善眼痛的康复和增加 退伍军人和非退伍军人的功能和生活质量相同。

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.