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

• 批准号: 10132338
• 负责人: CHRISTOPHER W TYLER
• 金额: $ 41.22万
• 依托单位: SMITH-KETTLEWELL EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 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/10132338
• 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

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.

创伤性脑损伤光敏感症的ERG频谱分析 摘要 脑震荡引起的光过敏，或创伤性光痛，可能是一个终身衰弱的问题。 适用于数百万轻度创伤性脑损伤(MTBI)病例中的60%以上。没有电流 对这种持续性光敏感的疼痛的解释和以前没有脑外伤影响的报道 视网膜处理。我们建议使用光调适视网膜电图(ERG)的频谱分析。 作为强度和波长的函数的反应以评估对视网膜的意外损害 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 光能脑损伤的暗视b波提示视锥细胞对视杆细胞的抑制 在正常情况下工作，这种抑制被脑部创伤的影响所阻断 光敏感度增强的病例。这些对以前不为人知的视网膜的新见解 创伤性光痛的机制表明，痛性光敏感性的主要原因是 由AII无长突细胞介导的杆状抑制，导致杆状细胞在较高的光照下过度激活。 在mTBI中，视杆过度激活增强光敏感性的新假说将被全面评估。 全场ERG随波长和光适应水平变化的范围研究。 为了充分描述连接杆和锥体的ERG波形的既定分量 通路反应，复杂的ERG波形将通过神经分析建模进行分析 将表征每个主要视网膜处理水平的ERG成分的方法 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 以及视杆和视锥感光系统的光视觉负响应(PhNR)作为函数 对照的光波长和光适应水平，以及作为光痛水平的函数的mTBI。在……里面 此外，黑色素系统的作用将根据光谱敏感度进行评估 持续的瞳孔大小评估在诱发诱因的条件下瞳孔大小不受影响的假设 创伤性光痛，因此不能补偿观察到的视杆敏感性的变化。 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，为精确规范记录的ERG波形提供基线 由于mTBI的影响而发生的变化。光适应视网膜电信号相关波形的变化 波形将为疼痛的光敏感性提供一个强大的非侵入性诊断生物标志物 外伤性光痛和mTBI的持续性视网膜效应。神经分析建模方法将 提供一种增强的方法来分析视网膜疾病的ERG波形变化 将军。