Save Sight Institute, The University of Sydney, NSW, Australia; Department of Health and Medical Sciences, Macquarie University, NSW, Australia.
Save Sight Institute, The University of Sydney, NSW, Australia.
Ophthalmology. 2019 Jun;126(6):801-810. doi: 10.1016/j.ophtha.2019.01.016. Epub 2019 Feb 1.
To compare functional and structural changes in the retina in patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS).
Cross-sectional study; biochemical study of human retinas.
A total of 181 participants, including 22 consecutive patients (44 eyes) with NMOSD, 131 patients (262 eyes) with multiple sclerosis (MS), and 28 normal subjects (56 eyes). In addition, 8 eyeballs from healthy donors were used for biochemical analysis.
Full-field electroretinography (ERG) and spectral-domain OCT were performed in all the subjects. Topography of AQP4 expression and Müller glial distribution were analyzed using Western blotting and immunohistochemistry.
Full-field ERG parameters, including amplitudes and peak times. Tissue volume of each of the retinal layers at the fovea by OCT segmentation. Levels of AQP4 expression at different retinal regions.
The b-wave amplitude was significantly reduced in patients with AQP4-IgG+ NMOSD in scotopic ERGs (compared with AQP4-IgG- subjects, patients with MS, and normal controls) but not in photopic ERGs. Further analysis showed that this b-wave change was mainly caused by reduction of the slow PII component, suggesting specific Müller cell dysfunction. We also found thinning of specific retinal layers at the fovea in patients with AQP4-IgG+ NMOSD, in the Henle fiber outer nuclear layer (HFONL) and the inner segment (IS) layer, but not in the inner nuclear layer (INL), outer plexiform layer (OPL), or outer segment (OS) layer. Furthermore, there was a significant association between foveal HFONL-IS complex thinning and scotopic b-wave amplitude reduction (P = 0.005∼0.01, fixed-effects model). Western blotting demonstrated that Müller cell-specific AQP4 was expressed at a higher level at the fovea than the peripheral retina. Immunohistochemical studies revealed that the specific foveal thinning reflected the topography of AQP4 expression and Müller glial distribution in the human macula.
This study provides in vivo structural and functional evidence of Müller glial dysfunction in eyes of patients with AQP4-IgG+ NMOSD. Topography of retinal structural change is supported by distribution of Müller cells and patterns of AQP4 expression. The study suggests that visual electrophysiology and retinal imaging could be useful biomarkers to assess the potential retinal astrocytopathy in NMOSD.
比较水通道蛋白 4 免疫球蛋白 G（AQP4-IgG）阳性视神经脊髓炎谱系障碍（NMOSD）和多发性硬化（MS）患者视网膜的功能和结构变化。
横断面研究；人视网膜的生化研究。
共纳入 181 名参与者，包括 22 例连续 NMOSD 患者（44 只眼）、131 例 MS 患者（262 只眼）和 28 名正常对照者（56 只眼）。此外，还使用 8 只来自健康供体的眼球进行了生化分析。
所有受试者均行全视野视网膜电图（ERG）和光谱域 OCT 检查。使用 Western blot 和免疫组化分析 AQP4 表达和 Müller 胶质细胞分布的拓扑结构。
全视野 ERG 参数，包括振幅和峰值时间。OCT 分割测量黄斑区各视网膜层的组织体积。不同视网膜区域 AQP4 表达水平。
在暗视条件下，NMOSD 患者的 AQP4-IgG+ NMOSD 患者的 b 波振幅明显降低（与 AQP4-IgG-患者、MS 患者和正常对照组相比），但在明视条件下无此改变。进一步分析表明，这种 b 波改变主要是由于慢 PII 成分减少所致，提示特定的 Müller 细胞功能障碍。我们还发现 AQP4-IgG+ NMOSD 患者的黄斑区特定视网膜层变薄，Henle 纤维外核层（HFONL）和内节（IS）层变薄，但内核层（INL）、外丛状层（OPL）和外节（OS）层无此改变。此外，黄斑区 HFONL-IS 复合体变薄与暗视 b 波振幅降低之间存在显著相关性（P=0.005∼0.01，固定效应模型）。Western blot 显示，Müller 细胞特异性 AQP4 在黄斑区的表达水平高于周边视网膜。免疫组化研究表明，特定的黄斑区变薄反映了人黄斑区 AQP4 表达和 Müller 胶质细胞分布的拓扑结构。
本研究提供了 AQP4-IgG+ NMOSD 患者眼内 Müller 胶质功能障碍的体内结构和功能证据。视网膜结构变化的拓扑结构与 Müller 细胞的分布和 AQP4 表达模式相吻合。研究表明，视觉电生理学和视网膜成像可能是评估 NMOSD 潜在视网膜星形胶质病的有用生物标志物。
