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; 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）是一种毁灭性的神经脱生性疾病，会导致年轻，中年的视觉障碍 以及老年人，导致生产力降低了，社会成本损失。当前的思维属性丢失 构成视神经的视网膜神经节细胞（RGC）的MS致死和功能障碍。但是，只有 视觉功能与RGC萎缩之间的弱相关性，一些没有RGC萎缩的患者有视力丧失， 尚未确定提示MS视力丧失的所有相关贡献​​者尚未确定。我们发现了结构 大多数有MS和少数人的视网膜中央凹绕区（FAZ）的特征 青光眼在光感受器层上呈阴影并与视觉功能相关。我们的发现有助于 解决理解视觉途径参与MS的差距，为诊断和治疗提供新的窗口 MS视力丧失。该项目研究了最近发现的MS和相关人的视网膜中发现的FAZ功能 使用自适应光学扫描光眼镜的疾病，高分辨率，无创，最先进的成像 技术。在第一个目标中，将使用MS定义中央视觉功能与FAZ功能之间的关系为 实验模型。先进的微度测定法将用于检验以下假设：光感受器阴影为 视力丧失的机制。在第二个目标中，FAZ功能的原因和组成将通过 MS，MS，青光眼与相关神经系统和相关神经系统和相关神经系统之间的横截面比较的纵向研究 前体内MS眼科疾病和组织病理学研究。在第三个目标中，快速成像协议将是 开发以更快地检测FAZ功能，并将其应用于估计FAZ功能的分布 在具有MS，青光眼，其他疾病和对照的人群中。这些观察结果将评估 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进步 了解MS的视力丧失，制定快速成像策略，以使对大型样本大小进行更广泛的研究 多个地点和评估FAZ特征是MS，青光眼和其他疾病的生物标志物。