Center of Neuroimmunology, Institut d'Investigacions Biomediques August Pi Sunyer, Barcelona, Spain.
Department of Ophthalmology, Hospital Clinic, University of Barcelona, Barcelona, Spain.
Invest Ophthalmol Vis Sci. 2021 May 3;62(6):11. doi: 10.1167/iovs.62.6.11.
Raman spectroscopy allows molecular changes to be quantified in vivo from the tissues like the retina. Here we aimed to assess the metabolic changes in the retina of patients with multiple sclerosis (MS).
We built a Raman spectroscopy prototype by connecting a scanning laser ophthalmoscope to a spectrophotometer. We defined the spectra of 10 molecules participating on energy supply, axon biology, or synaptic damage, which have been shown to be altered in the brain of patients with MS: cytochrome C, flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NADH), N-acetyl-aspartate (NAA), excitotoxicity, glutamate, amyloid β (Aβ), τ and α-synuclein (SNCA), phosphatidyl-ethanolamine, and phosphatidyl-choline. We studied these molecules in a prospective cohort of patients with MS, either in the chronic phase or during relapses of acute optic neuritis (AON).
Significant changes to all these molecules were associated with age in healthy individuals. There was a significant decrease in NADH and a trend toward a decrease in NAA in patients with MS, as well as an increase in Aβ compared with healthy controls. Moreover, NADH and FAD increased over time in a longitudinal analysis of patients with MS, whereas Aβ diminished. In patients with acute retinal inflammation due to AON, there was a significant increase in FAD and a decrease in SNCA in the affected retina. Moreover, glutamate levels increased in the affected eyes after a 6-month follow-up.
Alterations of molecules related to axonal degeneration are observed during neuroinflammation and show dynamic changes over time, suggesting progressive neurodegeneration.
拉曼光谱允许从视网膜等组织中定量检测分子变化。在这里，我们旨在评估多发性硬化症（MS）患者视网膜的代谢变化。
我们通过将扫描激光检眼镜连接到分光光度计来构建拉曼光谱原型。我们定义了参与能量供应、轴突生物学或突触损伤的 10 种分子的光谱，这些分子在 MS 患者的大脑中已经显示出改变：细胞色素 C、黄素腺嘌呤二核苷酸（FAD）、烟酰胺腺嘌呤二核苷酸（NADH）、N-乙酰天冬氨酸（NAA）、兴奋性毒性、谷氨酸、β-淀粉样蛋白（Aβ）、τ 和α-突触核蛋白（SNCA）、磷脂乙醇胺和磷脂酰胆碱。我们在 MS 患者的前瞻性队列中研究了这些分子，无论是在慢性期还是在急性视神经炎（AON）复发期间。
在健康个体中，所有这些分子的显著变化都与年龄相关。与健康对照组相比，MS 患者的 NADH 显著降低，NAA 呈下降趋势，Aβ 增加。此外，在 MS 患者的纵向分析中，NADH 和 FAD 随时间增加，而 Aβ 减少。在由于 AON 引起的急性视网膜炎症患者中，受影响视网膜中的 FAD 显著增加，SNCA 减少。此外，在 6 个月的随访后，受影响眼睛中的谷氨酸水平增加。
在神经炎症期间观察到与轴突变性相关的分子的改变，并随着时间的推移显示出动态变化，提示进行性神经退行性变。
