Department of Neuroinflammation, UCL Institute of Neurology, Queen Square, London, UK.
The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
Brain. 2020 Jul 1;143(7):1999-2008. doi: 10.1093/brain/awaa049.
Mitochondrial failure and hypoxia are key contributors to multiple sclerosis pathophysiology. Importantly, improving mitochondrial function holds promise as a new therapeutic strategy in multiple sclerosis. Currently, studying mitochondrial changes in multiple sclerosis is hampered by a paucity of non-invasive techniques to investigate mitochondrial function of the CNS in vivo. It is against this backdrop that the anterior visual system provides new avenues for monitoring of mitochondrial changes. The retina and optic nerve are among the metabolically most active structures in the human body and are almost always affected to some degree in multiple sclerosis. Here, we provide an update on emerging technologies that have the potential to indirectly monitor changes of metabolism and mitochondrial function. We report on the promising work with optical coherence tomography, showing structural changes in outer retinal mitochondrial signal bands, and with optical coherence angiography, quantifying retinal perfusion at the microcapillary level. We show that adaptive optics scanning laser ophthalmoscopy can visualize live perfusion through microcapillaries and structural changes at the level of single photoreceptors and neurons. Advantages and limitations of these techniques are summarized with regard to future research into the pathology of the disease and as trial outcome measures.
线粒体功能衰竭和缺氧是多发性硬化症病理生理学的关键因素。重要的是，改善线粒体功能有望成为多发性硬化症的一种新的治疗策略。目前，由于缺乏非侵入性技术来研究中枢神经系统的线粒体功能，因此研究多发性硬化症中的线粒体变化受到了阻碍。正是在这种背景下，前视系统为监测线粒体变化提供了新的途径。视网膜和视神经是人体代谢最活跃的结构之一，在多发性硬化症中几乎总是受到不同程度的影响。在这里，我们提供了一些新兴技术的最新进展，这些技术有可能间接监测代谢和线粒体功能的变化。我们报告了关于光学相干断层扫描的有前途的工作，该工作显示了外视网膜线粒体信号带的结构变化，以及关于光学相干血管造影术的工作，该技术可以定量测量微毛细血管水平的视网膜灌注。我们表明，自适应光学扫描激光检眼镜可以可视化微毛细血管中的实时灌注以及单个光感受器和神经元水平的结构变化。总结了这些技术的优缺点，以便将来对疾病的病理学进行研究，并作为试验的结果测量。
