中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (2): 521-533.doi: 10.4103/NRR.NRR-D-24-00685

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

光遗传学方法在神经组织再生中的应用

  

  • 出版日期:2026-02-15 发布日期:2025-05-20

Optogenetic approaches for neural tissue regeneration: A review of basic optogenetic principles and target cells for therapy

Davletshin Eldar1, *, Sufianov Albert2, 3, Ageeva Tatyana1 , Sufianova Galina4 , Rizvanov Albert1, 5, Mukhamedshina Yana1, 5, 6   

  1. 1 OpenLab Gene and Cell Technologies, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia;  2 Department of Neurosurgery, Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia;  3 Research and Educational Institute of Neurosurgery, Peoples’ Friendship University of Russia (RUDN), Moscow, Russia;  4 Department of Pharmacology, Tyumen State Medical University, Tyumen, Russia;  5 Division of Medical and Biological Sciences, Tatarstan Academy of Sciences;  6 Department of Histology, Cytology and Embryology, Kazan State Medical University, Kazan, Russia
  • Online:2026-02-15 Published:2025-05-20
  • Contact: Davletshin Eldar, PhD candicate, eldar.davletschin@gmail.com.
  • Supported by:
    This work was supported by a grant from the Russian Science Foundation, No. 23-75-10041 (to MY); https://rscf.ru/en/project/23-75-10041/ (to MY).

摘要:

光遗传学能够利用称为光蛋白的光敏蛋白精确控制神经活动,从而彻底改变了神经科学领域。文章讨论了光遗传学的基本原理,包括兴奋性和抑制性蛋白的激活,以及重组病毒载体等光遗传学模型的开发。文章的一个重要部分是介绍使用光遗传学工具的局限性,以及解决这些局限性的策略,包括使用腺相关病毒、细胞特异性启动子、修饰的视蛋白和生物发光光遗传学等方法。病毒重组载体,尤其是更有希望用于临床实践的腺相关病毒,在向细胞输送蛋白方面的应用正变得越来越多样化,这表明有可能创造出一种具有更灵活定制功能的工具,并有可能提高向靶细胞输送蛋白的准确性。这些载体的适应性是光遗传学研究的一个优势,因为它们可以通过使用细胞特异性启动子和不同的病毒血清型来限制蛋白的表达。此外,文章还探讨了光遗传学的各种细胞靶标,包括神经元、星形胶质细胞、小胶质细胞和许旺细胞,在这些细胞中使用特异性启动子表达光蛋白对于实现精确、高效的刺激至关重要。研究表明,分别对神经元和神经胶质细胞,尤其是不同表型的小胶质细胞、星形胶质细胞和许旺细胞进行光遗传刺激,可对神经系统疾病产生治疗效果。神经胶质细胞正逐渐成为神经疾病的治疗靶点。最后,这篇综述重点介绍了生物发光光遗传学这一新兴领域。在这一领域,光遗传学原理与生物发光蛋白相结合,可实时观察和操纵神经活动。通过将分子遗传学技术与生物发光技术相结合,研究人员能够高效、低创地监测神经元活动,并研究它们在各种生理和病理过程中的作用,这有助于拓展我们对中枢神经系统功能和神经系统疾病可塑性机制的认识,超越了传统的神经生物学方法。研究表明,在这些疾病的模型中,光遗传暴露可调节和增强运动轴突再生、完全感觉神经支配和加速神经肌肉功能的恢复,同时诱导运动神经元协调活动和神经重组的复杂模式因此,光遗传学方法在中枢神经系统的治疗干预方面具有巨大潜力,可实现对神经回路的精确控制,并有可能治疗神经系统疾病,特别是脊髓损伤、周围神经损伤和其他神经退行性疾病。

https://orcid.org/0000-0001-8784-3200 (Davletshin Eldar)

关键词: 腺相关病毒, 星形胶质细胞, 生物发光光遗传学, 通道发光素 Halorhodopsins, 小胶质细胞, 神经元, 神经干细胞, 光遗传学, 寡突胶质细胞

Abstract: Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins. This review article discusses the fundamental principles of optogenetics, including the activation of both excitatory and inhibitory opsins, as well as the development of optogenetic models that utilize recombinant viral vectors. A considerable portion of the article addresses the limitations of optogenetic tools and explores strategies to overcome these challenges. These strategies include the use of adeno-associated viruses, cell-specific promoters, modified opsins, and methodologies such as bioluminescent optogenetics. The application of viral recombinant vectors, particularly adeno-associated viruses, is emerging as a promising avenue for clinical use in delivering opsins to target cells. This trend indicates the potential for creating tools that offer greater flexibility and accuracy in opsin delivery. The adaptations of these viral vectors provide advantages in optogenetic studies by allowing for the restricted expression of opsins through cellspecific promoters and various viral serotypes. The article also examines different cellular targets for optogenetics, including neurons, astrocytes, microglia, and Schwann cells. Utilizing specific promoters for opsin expression in these cells is essential for achieving precise and efficient stimulation. Research has demonstrated that optogenetic stimulation of both neurons and glial cells—particularly the distinct phenotypes of microglia, astrocytes, and Schwann cells—can have therapeutic effects in neurological diseases. Glial cells are increasingly recognized as important targets for the treatment of these disorders. Furthermore, the article emphasizes the emerging field of bioluminescent optogenetics, which combines optogenetic principles with bioluminescent proteins to visualize and manipulate neural activity in real time. By integrating molecular genetics techniques with bioluminescence, researchers have developed methods to monitor neuronal activity efficiently and less invasively, enhancing our understanding of central nervous system function and the mechanisms of plasticity in neurological disorders beyond traditional neurobiological methods. Evidence has shown that optogenetic modulation can enhance motor axon regeneration, achieve complete sensory reinnervation, and accelerate the recovery of neuromuscular function. This approach also induces complex patterns of coordinated motor neuron activity and promotes neural reorganization. Optogenetic approaches hold immense potential for therapeutic interventions in the central nervous system. They enable precise control of neural circuits and may offer new treatments for neurological disorders, particularly spinal cord injuries, peripheral nerve injuries, and other neurodegenerative diseases.

Key words: adeno-associated virus, astrocytes, bioluminescent optogenetics, channelrhodopsins, halorhodopsins, microglia, neural stem cells, neurons, oligodendrocyte, optogenetics