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.

项目摘要 多发性硬化症（MS）是一种严重的神经退行性疾病，主要影响青、中年人的视力 以及老年人，从而导致生产力的大量损失和社会成本。目前认为视力丧失是由于 MS导致包括视神经的视网膜神经节细胞（RGC）的死亡和功能障碍。然而，只有 视功能与RGC萎缩的相关性较弱，部分无RGC萎缩的患者视力下降， 这表明尚未确定MS中视力丧失的所有相关因素。我们发现了结构性的 大多数MS患者和少数MS患者的视网膜中央凹无血管区（FAZ）的特征 在感光层上投射阴影并与视觉功能相关的青光眼。我们的发现有助于 解决在理解MS视觉通路参与方面的差距，为诊断和治疗提供新的窗口 该项目研究了最近发现的FAZ功能在视网膜的人与MS和相关 疾病使用自适应光学扫描光检眼镜，高分辨率，非侵入性，国家的最先进的成像 法在第一个目标中，将使用MS定义中央视觉功能和FAZ特征之间的关系， 实验模型。先进的微视野检查将用于测试感光器阴影是 视力丧失的机制。在第二个目标的原因和组成的FAZ功能将推断通过 MS患者的纵向研究，MS、青光眼和相关神经系统疾病之间的横断面比较， 眼科疾病和离体MS眼睛的组织病理学研究。在第三个目标中，快速成像协议将是 开发了一种快速检测FAZ特征的方法，这些方法将用于估计FAZ特征的分布 在患有多发性硬化症、青光眼、其他疾病和对照的人群中。这些意见将评估候选人的资格。 FAZ通过定义特异性作为MS的生物标志物。这项研究的直接影响将是 了解MS中的视力丧失，开发快速成像策略，以实现更广泛的大样本量研究， 多个站点和评估FAZ功能作为MS，青光眼和其他疾病的生物标志物。