基于多模态磁共振的原发性开角型青光眼脑改变及机制研究

Glaucoma is a worldwide leading cause of irreversible vision loss. Primary open-angle glaucoma (POAG) is the most common form. Although the pathogenesis of POAG is not fully understood, the level of intraocular pressure is related to retinal ganglion cell death. However, it was reported that intraocular pressure was normal in nearly 50% of individuals with POAG. Diagnosis is frequently delayed, because it may by asymptomatic until a relatively late stage. On the other hand, the disease progression is not slowed by reduction of intraocular pressure in some POAG patients. Thus, it is important to clarify the pathogenesis of POAG and improve treatment outcomes. Increasing evidence has accumulated that POAG involves multiple brain regions, indicating that neurodegeneration may be the initiating feature of the pathogenesis. On this account, we hypothesize that POAG is a neurodegenerative disease which involves visual pathway and multiple associated brain regions, and the alteration of brain correlates with severity of the disease. Therefore, multimodal magnetic resonance imaging study, including diffusion kurtosis imaging (DKI), resting state functional MRI (rs-fMRI), magnetic resonance perfusion imaging of arterial spin labeling (3D-ASL) and amide proton transfer (APT), will be employed to analyze the alteration of brain in POAG patients, and the relationship between abnormality of brain and disease severity. These results will be expected to clarify the brain alteration and the mechanism in POAG, and to provide evidence for early detection of the disease and new treatment strategy.

青光眼是全球首位不可逆性致盲眼病。原发性开角型青光眼（POAG）是最常见青光眼类型，其发病机制不明，目前认为眼压升高导致视网膜神经节细胞死亡和视神经损害是主要发病机制，但约一半患者眼压正常，确诊时已为中晚期，且降低眼压后，即使高眼压的患者视野损害仍在继续发展，因此，弄清其发病机制对进一步认清该病本质及提高诊治水平至关重要。近年来，越来越多的结果显示POAG同时累及多个脑区的结构与功能，提示神经退行性改变可能是其发病机制。有鉴于此，我们提出以下科学假说：POAG是神经退行性疾病，导致视觉传导通路及多个相关脑区发生改变，并与疾病严重程度相关。拟采用包括弥散峰度成像和酰胺质子转移成像等新技术在内的多模态磁共振成像研究不同病程POAG患者全脑微细结构、功能、灌注和代谢变化特点及其与疾病严重程度的关系，验证假说，阐明POAG脑改变及发生机制，为早诊早治及提出新治疗方案提供指导和参考依据。

原发性开角型青光眼（POAG）是最常见的青光眼类型，其发病机制不明，近年来越来越多的证据提示POAG累及视觉通路内、外多个脑区，提示神经退行性改变是其重要的发病机制。本项目纳入患者90例，正常对照组40例，基于POAG 是神经退行性疾病的假说，采用多模态脑功能成像研究POAG脑微细结构、功能、灌注等改变及其与疾病严重程度和眼科临床指标的关系。研究发现：POAG患者存在视觉通路内、外广泛的白质微结构的损伤，而且，患者从初级视觉皮层到高级皮层的信息流减少，自上而下的处理增强；其白质损伤及信息流改变与视皮质的微结构损伤有关；为POAG脑微结构损伤及脑功能重组提供理论依据。POAG患者视觉皮层半球间镜像同伦功能连接及解剖连接减低并与疾病严重程度相关；视觉网络枕极成分与另两个成分功能连接减低，并且视觉网络与默认网络成分间的功能连接重组；基于拓扑分析发现患者核心节点转移，涉及视觉、感觉及运动、认知及情绪系统，反映了POAG患者的脑网络重组。早-中期POAG患者的视觉皮层即已出现异常的血流灌注，另外还发现神经血管单元复合体的损伤不仅累及视觉皮层，还累及多个高级认知功能区；视觉区的损伤与视野缺损显著相关。该研究阐明了POAG患者脑微细结构、功能、灌注改变及其与疾病严重程度的关系，验证了POAG 神经退行性疾病的假说，为疾病早期诊断、开发新的治疗方案提供指导和参考依据。