Human Ocular Surface Sensory Processing

你的眼睛感觉如何？多年来，这个模棱两可的问题推动了我的实验室所做的大部分工作。这个问题可能是关于你眼球前部的感觉，而答案可能是“我的眼睛灼热”。另一方面，这个问题可能是关于什么神经机制可以感知环境，答案可能包括“化学伤害性感受器感知泪液中PH值的变化”。对这一问题的后一种解释构成了这项建议的框架。在人类中，我们对感觉解剖学和生理学几乎一无所知，对眼睛表面如何感知环境仍然相对知之甚少：目标集中在了解人类眼睛的感觉上，特别是使用我们已经部分开发并继续改进的仪器，计算机化气动(贝尔蒙特)感觉仪。使用它，我们能够提供校准的、系统变化的机械(流动)、化学(添加二氧化碳)和热(冷却)刺激。目标1)利用信号检测理论(SDT)，开发在人类中使用感觉指标的技术，这些指标不太容易受到阈值和阈值上过程中固有的(与疼痛相关的)偏差的影响：这将使用多标准-多刺激方法来完成。受试者将收到4个系统变化的刺激强度中的1个(根据每个受试者的阈值进行调整)，并将使用一个按钮框做出回应，该按钮框使用5分制来衡量他们对刺激存在的确定性。我们将得出每种刺激类型和眼表位置的接收器操作特征曲线，并对数据进行比较。2)绘制整个眼表的阈值周围和阈值以上的机械、化学和热(主要是冷却)过程：我们将特别关注结膜，因为这部分眼表几乎被完全忽略：将这些感觉数据与使用共焦显微镜和超高分辨率光学相干断层扫描(OCT)获得的结构和形态信息(特别是神经)相关联。3)检查眼表阈值和阈值上刺激是如何处理的，并驱动泪液、瞳孔缩小/散瞳、结膜血管扩张(红肿)的局部眼自主神经反应：刺激强度将使用d‘来衡量，或在单独的实验中使用阈值上的强度。我们将模拟这些客观反应如何与刺激引起的疼痛感觉相关，以确定这些反射反应是否可以用作感官效应的替代。这将使科学家和临床医生能够使用这项技术客观地确定疼痛反应，甚至确定患者是否有意识。长期目标1)扩大对人类如何处理眼表信息的理解。2)提供客观测量眼痛的策略/工具。3)为眼表疼痛和不适提供治疗。

How do your eyes feel? This ambiguous question has driven much of the work done in my lab for many years. The question might be about the sensations occurring at the front of your eye and the answer might be "my eyes burn". On the other hand, the question might be about what neural mechanisms sense the environment and an answer might include "chemo nociceptors sense change in pH in tears". The latter interpretation of the question forms the framework for this proposal. In humans we know almost nothing about the sensory anatomy & physiology, and still relatively little about of how the ocular surface senses the environment: The objectives are centred on understanding how human eyes feel using, in particular, an instrument we have partly developed and continue to refine, the computerised pneumatic (Belmonte) esthesiometer. Using it, we are able to deliver calibrated, systematically varying mechanical (flow), chemical (added CO2) and thermal (cooling) stimuli. Objectives 1) to develop techniques using sensory metrics in humans that are less susceptible to (pain-related) biases inherent in threshold & suprathreshold processes, using Signal Detection Theory (SDT): This will be done using a multiple criterion-multiple stimulus method. Subjects will receive 1 of 4 systematically varying stimulus intensities (scaled according to each subject's threshold) and will respond with a button box using a 5 point scale about their certainty about the stimulus presence. We will derive receiver operating characteristic curves for each stimulus type and ocular surface location and compare the data. 2) map circum-threshold and suprathreshold mechanical, chemical and thermal (principally cooling) processes across the ocular surface: We will focus particularly on the conjunctiva because this part of the ocular surface has been almost completely ignored: Relate these sensory data to structural and morphometric information (particularly of the nerves) obtained using confocal microscopy and ultra-high resolution optical coherence tomography (OCT). 3) examine how ocular surface threshold and suprathreshold stimulation is processed and drives local ocular autonomic responses of lacrimation, pupillary miosis/mydriasis, conjunctival vessel dilation (redness): Stimulus intensities will be scaled using d' or in a separate experiment using suprathreshold intensities. We will model how these objective responses are related to the painful sensations induced by the stimuli to determine if these reflex responses can be used as a proxy for the sensory effects. This will enable scientists and clinicians to use this technique to determine pain responses objectively and even determine if patients are conscious. Long term goals 1) To extend the understanding of how humans process ocular surface information. 2) To provide strategies/instruments to measure ocular pain objectively. 3) To provide treatments for ocular surface pain and discomfort.