中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (5): 1011-1012.doi: 10.4103/1673-5374.324841

• 观点:退行性病与再生 • 上一篇    下一篇

肌萎缩侧索硬化症，一种累及视网膜的神经退行性运动神经元疾病

  

  • 出版日期:2022-05-15 发布日期:2021-11-08

Amyotrophic lateral sclerosis, a neurodegenerative motor neuron disease with retinal involvement

Ana I. Ramírez, Rosa de Hoz, Pilar Rojas, Juan J. Salazar*   

  1. Instituto de Investigaciones Oftalmológicas Ramón Castroviejo. Universidad Complutense de Madrid, Madrid, Spain  (Ramírez AI, de Hoz R, Rojas P, Salazar JJ) 
    Facultad de Óptica y Optometría. Departamento de Inmunología, Oftalmología y ORL. Universidad Complutense de Madrid, Madrid, Spain (Ramírez AI, de Hoz R, Salazar JJ)
    Hospital General Universitario Gregorio Marañón, Instituto Oftálmico de Madrid, Madrid, Spain (Rojas P) 
  • Online:2022-05-15 Published:2021-11-08
  • Contact: Juan J. Salazar, PhD, jjsalazar@med.ucm.es.
  • Supported by:
    The present work was supported by: (i) the Ophthalmological Network OFTARED (RD16/0008/0005)‚ of the Institute of Health of Carlos III of the Spanish Ministry of Economy (to AIR); and (ii) the Network RETiBRAIN (La retina un modelo para investigar Neuroprotección en patologías del Sistema Nervioso Central) (RED2018-102499-T) of the Spanish Ministry of Science, Innovation, and Universities (to RDH and JJS).

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摘要： Neural Regen Res：肌萎缩侧索硬化不仅损害运动神经元，还影响视网膜组织
肌萎缩侧索硬化是一种神经退行性疾病，会损害运动神经元、脊髓、小脑和大脑的某些区域。最近研究表明，肌萎缩侧索硬化也可以影响视觉系统。肌萎缩侧索硬化患者通常不会抱怨视觉问题，因此关注视觉通路的研究很少。肌萎缩侧索硬化和眼睛的早期工作与动眼神经功能和视觉通路分析有关，视觉诱发电位被用于研究这种疾病。随后出现了一些分析视觉功能的研究，包括视力、视野、对比敏感度等测试。在神经退行性疾病中，观察到大脑中发生的变化也发生在视网膜中。视网膜的变化可以通过眼科广泛使用的诊断测试来检测，即光学相关断层扫描。最近，该技术已被用于分析各种神经退行性疾病（例如阿尔茨海默病、帕金森病，甚至肌萎缩侧索硬化）中发生的视网膜和视神经变化，并可帮助他们进行诊断和随访。在肌萎缩侧索硬化患者的视网膜中，光学相关断层扫描已证明视乳头周围视网膜神经纤维层、内核层和外核层的视网膜变薄，这可能与神经退行性过程有关。 在肌萎缩侧索硬化患者的视网膜上，观察到视网膜神经节细胞轴突的丢失，这可以解释光学相关断层扫描观察到的黄斑变薄。
来自西班牙马德里康普顿斯大学的Juan J. Salazar团队认为，在神经退行性疾病（例如阿尔茨海默病和帕金森病、青光眼）的发病机制中，神经炎症起着重要作用。在神经系统的炎症过程中，小胶质细胞响应损伤而被激活，发生形态变化，增殖和迁移。此外，激活的小胶质细胞可以存在于两个不同激活极端之间的连续体中，即 M1 和 M2 表型。 M1 或促炎表型的特征是释放炎症介质，例如一氧化氮和活性氧，以及促炎细胞因子，包括干扰素 γ、肿瘤坏死因子-α、白细胞介素 (IL)-1β、IL-6和 IL-12。所有这些因素都会产生强烈的炎症反应，如果是慢性的，会导致神经元死亡。而M2表型则产生相反的作用，释放脑源性神经营养因子、神经营养因子、胶质细胞源性神经营养因子等神经营养因子，以及抗炎细胞因子，主要是IL-4、IL-10和IL-13，可以控制炎症过程，促进神经元存活。总之，肌萎缩侧索硬化不仅会损害运动神经元，还会影响视网膜组织，伴有小胶质细胞激活和视网膜神经节细胞丢失。这些视网膜变化已被光学相关断层扫描记录在肌萎缩侧索硬化患者身上，可作为生物标志物，帮助肌萎缩侧索硬化患者的诊断和随访，以及通过使用简单的方式如光学相关断层扫描监测不同治疗的疗效来测试不同治疗的疗效。
   文章在《中国神经再生研究（英文版）》杂志2022年 5 月 5  期发表。

Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that damages the motor neurons, the spinal cord, the cerebellum, and some areas of the brain. However, more recent studies show that it can also affect the visual system, for example, through oculomotor and visual pathways. ALS patients do not usually complain of visual problems, so studies focusing on the visual pathway are scarce. Early work on ALS and the eye was related to oculomotor function and visual pathway analysis, with visually evoked potentials being used to study the disease. Subsequently, some works have appeared that analyze visual function, with tests such as visual acuity, visual field, and contrast sensitivity. Furthermore, in neurodegenerative diseases, it is observed that the changes that occur in the brain also occur in the retina, with this nervous tissue being considered as a “window to the brain” (MacCormick et al., 2015). The changes in the retina can be detected by a widely used diagnostic test in ophthalmology, namely optical coherence tomography (OCT). Recently, this technique has been used for the analysis of the retinal and optic nerve changes that occur in various neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and even ALS, and can serve to help in their diagnosis and follow-up (Salobrar-García et al., 2016; Rojas et al., 2019). In the retina of ALS patients, OCT has demonstrated retinal thinning in the peripapillary retinal nerve fiber layer, inner nuclear layer, and outer nuclear layer, which may be related to neurodegenerative processes (Volpe et al., 2015; Rohani et al., 2018; Rojas et al., 2019). This fact has been confirmed by histopathological studies performed by Volpe et al. on retinas of ALS patients and they observed a loss of retinal ganglion cell axons, which would explain the macular thinning observed by OCT (Volpe et al., 2015). In addition, a study in early spinal-onset ALS patients without ocular disease demonstrated retinal thickening, through significant increases in the macular thickness in the temporal and inferior areas of the inner macular ring, suggesting that the thickening may be due to microglial activation during the neuroinflammatory process (Rojas et al., 2019).