Beyond ganglion cells: Novel foveal avascular zone features in MS with implications for vision loss

超越神经节细胞：多发性硬化症中新的中心凹无血管区特征对视力丧失的影响

• 批准号: 10522605
• 负责人: Heather Elspeth Moss
• 金额: $ 52.77万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10522605
• 关键词: Address; Adult; Affect; Age; Atrophic; Autopsy; Behavior; Biological; Biological Markers; Blindness; Brain; Caring; Cessation of life; Clinic; Clinical; Clinical Research; Comparative Study; Complement; Confocal Microscopy; Coupled; Detection; Diagnosis; Disease; Disease Progression; Elderly; Electroretinography; Etiology; Experimental Models; Eye; Functional disorder; Future; Glaucoma; Glean; High Prevalence; Human; Image; Imaging Device; Imaging Techniques; Immunofluorescence Immunologic; In Vitro; Inflammatory; Investigation; Lesion; Light; Location; Longitudinal Studies; Measurement; Measures; Methods; Microscopy; Minority Groups; Monitor; Multiple Sclerosis; Nature; Nerve Degeneration; Neurodegenerative Disorders; Neurologic; Ophthalmoscopy; Optic Nerve; Pathologic; Pathology; Patients; Persons; Phenotype; Photoreceptors; Physicians; Population; Productivity; Protocols documentation; Quality of life; Research; Research Personnel; Resolution; Retina; Retinal Ganglion Cells; Sample Size; Sampling; Scanning; Site; Societies; Specificity; Spinal Cord; Structure; Study Subject; Symptoms; Testing; Thinking; Time; Translations; Vision; Visual; Visual Acuity; Visual Pathways; Visual impairment; Work; adaptive optics; aged; base; candidate marker; clinical predictors; clinically relevant; cost; disability; disorder control; feature detection; ganglion cell; imaging biomarker; in vivo; life time cost; meetings; middle age; nervous system disorder; novel; retinal imaging

PROJECT SUMMARY Multiple sclerosis (MS) is a devastating neuro-degenerative disease that causes visual impairment in young, middle aged and older adults with resulting substantial lost productivity and cost to society. Current thinking attributes vision loss in MS to death and dysfunction of the retinal ganglion cells (RGCs) that comprise the optic nerve. However, there is only weak correlation between visual function and RGC atrophy, and some patients without RGC atrophy have vision loss, suggesting that all relevant contributors to vision loss in MS have not been identified. We have discovered structural features in the foveal avascular zone (FAZ) of retinas of the majority people with MS and a minority of people with glaucoma that cast a shadow on the photoreceptor layer and correlate with visual function. Our discovery contributes to addressing gaps in understanding visual pathway involvement in MS, offering new windows into diagnosis and treatment of vision loss in MS. This project studies the recently discovered FAZ features in retinas of people with MS and related diseases using adaptive optics scanning light ophthalmoscopy, a high resolution, non-invasive, state-of-the-art imaging technique. In the first aim, the relationship between central visual function and FAZ features will be defined using MS as an experimental model. Advanced microperimetry will be used to test the hypothesis that photoreceptor shadowing is the mechanism of vision loss. In the second aim the cause and composition of the FAZ features will be inferred through longitudinal studies of people with MS, cross sectional comparison between MS, glaucoma and related neurological and ophthalmic diseases and histopathological study of ex-vivo MS eyes. In the third aim rapid imaging protocols will be developed to enable faster detection of FAZ features and these will be applied to estimate the distributions of FAZ features in the populations with MS, glaucoma, other diseases and controls. These observations will evaluate the candidacy of the FAZ features as biomarkers of MS by defining specificity. The immediate impact of this research will be advancing understanding of vision loss in MS, developing rapid imaging strategies to enable broader study of large sample sizes at multiple sites and evaluating FAZ features as biomarkers in MS, glaucoma and other disease.

项目概要 多发性硬化症 (MS) 是一种毁灭性的神经退行性疾病，会导致年轻、中年人视力障碍 和老年人，从而导致生产力严重损失和社会成本。目前的想法将视力丧失归因于 MS 导致构成视神经的视网膜神经节细胞 (RGC) 死亡和功能障碍。然而，只有 视功能与RGC萎缩相关性较弱，部分无RGC萎缩的患者出现视力下降， 这表明导致多发性硬化症视力丧失的所有相关因素尚未确定。我们发现了结构性 大多数多发性硬化症患者和少数多发性硬化症患者视网膜中央凹无血管区 (FAZ) 的特征 青光眼在感光层上投射阴影并与视觉功能相关。我们的发现有助于 弥补对多发性硬化症视觉通路参与理解的差距，为诊断和治疗提供新的窗口 MS 中的视力丧失。该项目研究最近发现的多发性硬化症及相关患者视网膜中的 FAZ 特征 使用自适应光学扫描光检眼镜检查疾病，这是一种高分辨率、非侵入性、最先进的成像技术 技术。在第一个目标中，中央视觉功能和 FAZ 特征之间的关系将使用 MS 定义为 一个实验模型。先进的显微视野测量法将用于检验光感受器阴影的假设 视力丧失的机制。在第二个目标中，FAZ 特征的原因和组成将通过以下方式推断： 对多发性硬化症患者的纵向研究，多发性硬化症、青光眼及相关神经系统和疾病之间的横断面比较 眼科疾病和离体多发性硬化症眼的组织病理学研究。在第三个目标中，快速成像协议将是 开发用于更快地检测 FAZ 特征，这些将用于估计 FAZ 特征的分布 患有多发性硬化症、青光眼、其他疾病和控制的人群。这些观察结果将评估候选人的候选资格 FAZ 通过定义特异性而成为 MS 的生物标志物。这项研究的直接影响将不断推进 了解 MS 中的视力丧失，开发快速成像策略，以便能够对大样本量进行更广泛的研究 多个位点并评估 FAZ 特征作为多发性硬化症、青光眼和其他疾病的生物标志物。