Human Ocular Surface Sensory Processing

人眼表面感觉处理

• 批准号: RGPIN-2021-03071
• 负责人: Simpson, Trefford
• 金额: $ 2.04万
• 依托单位: University of Waterloo
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=742362
• 关键词: Human; Ocular; Surface; Sensory; Processing

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.

你的眼睛感觉如何？多年来，这个模棱两可的问题推动了我实验室的大部分工作。这个问题可能是关于你眼前发生的感觉，答案可能是“我的眼睛燃烧”。另一方面，问题可能是关于什么神经机制感知环境，答案可能包括“化学伤害感受器感知眼泪中pH值的变化”。对这一问题的后一种解释构成了这一建议的框架。在人类中，我们对感觉解剖学和生理学几乎一无所知，对眼表如何感知环境也知之甚少：我们的目标集中在了解人眼的感觉，特别是使用我们部分开发并继续改进的仪器，计算机化气动（贝尔蒙特）触觉计。使用它，我们能够提供校准的，系统变化的机械（流量），化学（添加CO2）和热（冷却）刺激。目标1）使用信号检测理论（SDT），开发使用人类感觉指标的技术，这些技术不易受阈值和阈上过程中固有的（疼痛相关）偏差的影响：这将使用多标准-多刺激方法完成。受试者将接受4种系统变化的刺激强度中的1种（根据每个受试者的阈值进行缩放），并将使用关于其对刺激存在的确定性的5点量表用按钮框进行响应。我们将推导出每种刺激类型和眼表位置的接收器工作特性曲线，并比较数据。2)绘制整个眼表的阈外和阈上机械、化学和热（主要是冷却）过程：我们将特别关注结膜，因为眼表的这一部分几乎被完全忽略：将这些感觉数据与使用共聚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）联系起来。3)检查眼表面阈值和阈上刺激如何被处理并驱动流泪、瞳孔缩小/瞳孔散大、结膜血管扩张（发红）的局部眼自主反应：在使用阈上强度的单独实验中，将使用d'或缩放刺激强度。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代理。这将使科学家和临床医生能够使用这种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）扩展对人类如何处理眼表信息的理解。 2)提供客观测量眼部疼痛的策略/工具。3)为眼表疼痛和不适提供治疗。