Spectral ERG Analysis of Hypersensitivity to Light in Traumatic Brain Injury

创伤性脑损伤中光过敏的光谱 ERG 分析

基本信息

批准号：
9973964
负责人：
CHRISTOPHER W TYLER
金额：
$ 42.49万
依托单位：
SMITH-KETTLEWELL EYE RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9973964
关键词：
Affect Amacrine Cells Behavior Biological Markers Brain Concussion Cells Chronic Clinical Complement Complex Cone Cone dystrophy Data Development Diagnostic Electroretinography Equilibrium Etiology Evaluation Eye Ganglion Cell Layer Goals Human Hypersensitivity Individual Injury Life Light Light Adaptations Measurement Measures Mediating Medical Methodology Modality Modeling Nature Non-linear Models Nonlinear Dynamics Pain Pathway Analysis Pathway interactions Persistent pain Photophobia Photoreceptors Pigment Epithelium Predisposition Protocols documentation Publications Pupil Rehabilitation therapy Reporting Retina Retinal Cone Retinal Diseases Rod Role Source Stimulus System Testing Traumatic Brain Injury Variant Vertebrate Photoreceptors Visual design diagnostic biomarker insight interest light intensity melanopsin mild traumatic brain injury noninvasive diagnosis novel response retinal damage

项目摘要

Spectral ERG analysis of hypersensitivity to light in traumatic brain injury Abstract Concussion-induced hypersensitivity to light, or traumatic photalgia, can be a lifelong debilitating problem for upwards of 60% of the millions of mild Traumatic Brain Injury (mTBI) cases. There is no current explanation for the pain of this persistent light sensitivity and no previous report of brain trauma affecting retinal processing. We propose to employ spectral analysis of light-adapted electroretinographic (ERG) responses as a function of intensity and wavelength to assess unsuspected damage to the retina of the human eye and determine its retinal-cell source. Our preliminary data show a shift from a photopic to a scotopic b-wave in photalgic brain trauma, which implies both that there is rod suppression by cones operating under normal conditions and that this suppression is blocked by the effects of the brain trauma in the cases of enhanced light sensitivity. These novel insights into the previously unknown retinal mechanisms of traumatic photalgia suggest that a primary etiology of the painful light sensitivity is loss of rod suppression mediated by AII amacrine cells, causing overactivation of the rods at higher light levels. The novel hypothesis of rod overactivation in enhanced light sensitivity in mTBI will be evaluated in a full- scope study of the full-field ERG as a function of wavelength and light adaptation level. To fully characterize the established components of the ERG waveforms of the conjoint rod and cone pathway responses, the complex ERG waveforms will be analyzed by a neuroanalytic modeling approach that will characterize the ERG components from each of the main retinal processing levels and their interactions across the range of stimulus conditions. In particular, we will track the a-wave, b-wave and photopic negative response (PhNR) of both the rod and the cone photoreceptor systems as a function of both light wavelength and light adaptation level for controls and mTBI as a function of photalgia level. In addition, the role of the melanopsin system will be assessed in terms of the spectral sensitivity of the sustained pupil size to assess the hypothesis that pupil size is not affected under conditions that induce traumatic photalgia, and hence does not compensate for the observed changes in rod sensitivity. The neuroanalytic model will allow the effective control ERG waveform to be computed for any degree of photalgic intensity setting, providing a baseline for precise specification of the recorded ERG waveform changes due to the effects of the mTBI. The correlated waveform changes in the light-adapted ERG waveforms will provide a powerful non-invasive diagnostic biomarker for the painful light sensitivity of traumatic photalgia and the persistent retinal effects of mTBI. The neuroanalytic modeling approach will provide an enhanced methodology for the analysis of ERG waveform changes in retinal diseases in general.

创伤性脑损伤光过敏的光谱 ERG 分析抽象的脑震荡引起的光过敏或外伤性眼痛可能会导致终生的衰弱问题数百万轻度创伤性脑损伤 (mTBI) 病例中 60% 以上的患者。没有电流对这种持续光敏感性造成的疼痛的解释以及之前没有脑外伤影响的报道视网膜处理。我们建议采用光适应视网膜电图（ERG）的光谱分析响应作为强度和波长的函数，以评估对视网膜的意外损伤人眼并确定其视网膜细胞来源。我们的初步数据显示从明视到明视的转变光性脑外伤中的暗视 b 波，这意味着视锥细胞对视杆细胞有抑制作用在正常条件下工作，并且这种抑制被脑外伤的影响所阻断光敏感性增强的情况。这些对以前未知的视网膜的新颖见解外伤性光痛的机制表明，疼痛性光敏感性的丧失是造成疼痛的主要原因。由所有无长突细胞介导的视杆细胞抑制，导致视杆细胞在较高光照水平下过度激活。 mTBI 中视杆细胞过度激活增强光敏感性的新假设将在全面评估中进行评估。作为波长和光适应水平的函数的全场 ERG 的范围研究。充分表征联合杆和锥体 ERG 波形的已建立组件通路反应，复杂的 ERG 波形将通过神经分析模型进行分析该方法将描述每个主要视网膜处理级别的 ERG 组件的特征，以及它们在各种刺激条件下的相互作用。特别是，我们将跟踪 a 波、b 波视杆细胞和视锥细胞感光系统的明视负响应（PhNR）作为函数控制和 mTBI 的光波长和光适应水平作为视痛水平的函数。在此外，还将根据黑视蛋白系统的光谱灵敏度来评估其作用。持续的瞳孔大小来评估瞳孔大小在诱导条件下不受影响的假设外伤性视痛，因此不能补偿观察到的杆敏感性变化。神经分析模型将允许计算任何程度的有效控制 ERG 波形光能强度设置，为记录的 ERG 波形的精确规范提供基线由于 mTBI 的影响而发生变化。光适应 ERG 中的相关波形变化波形将为痛苦的光敏感性提供强大的非侵入性诊断生物标志物创伤性眼痛和 mTBI 的持续视网膜影响。神经分析建模方法将为分析视网膜疾病中的 ERG 波形变化提供增强的方法一般的。