中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (10): 1911-1920.doi: 10.4103/1673-5374.308069

• 综述:视神经损伤修复保护与再生 • 上一篇    下一篇

间隙连接在视网膜细胞死亡和神经调节中的作用

  

  • 出版日期:2021-10-15 发布日期:2021-03-18

The role of gap junctions in cell death and neuromodulation in the retina

Gergely Szarka1, 2, 3, #, Márton Balogh1, 2, 3, #, Ádám J. Tengölics1, 2, 3, Alma Ganczer1, 2, 3, Béla Völgyi1, 2, 3, 4, Tamás Kovács-Öller1, 2, 4, *   

  1. 1János Szentágothai Research Centre, University of Pécs, Pécs, Hungary; 2Retinal Electrical Synapses Research Group, National Brain Research Program (NAP 2.0), Hungarian Academy of Sciences, Budapest, Hungary; 3Department of Experimental Zoology and Neurobiology, University of Pécs, Pécs, Hungary; 4Medical School, University of Pécs, Pécs, Hungary
  • Online:2021-10-15 Published:2021-03-18
  • Contact: Tamás Kovács-Öller, PhD, kovacstx@gmail.com.
  • Supported by:
    This work was supported by the Hungarian Brain Research Program 2 (2017-1.2.1.-NKP-2017) (to BV), by the NKFI (OTKA NN128293) from the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TAMOP-4.2.4.A/2-11/1-2012-0001 National Excellence Program (to BV) and by the ÚNKP-20-3-I-PTE-472 New National Excellence Program of the Ministry for Innovation and Technology (to GS).

摘要:

Neural Regen Res间隙连接是视网膜损伤后挽救神经细胞的可能途径

     间隙连接是神经调节和再生的新靶点,直接连接健康和/或病变细胞,在病理生理学中发挥着重要作用。由于它们对大分子具有渗透性,能够穿过细胞屏障,因此它们在疾病中表现出作为病因和治疗靶点的双重性。视觉感知的部位是视网膜,我们迫切需要新的工具来辅助视网膜再生,或者至少减慢削弱视力的现有疾病。神经元细胞(神经节细胞,无长突细胞,双极细胞,水平细胞和感光细胞)和非神经元细胞(星形细胞,小胶质细胞和穆勒细胞)都倾向于形成间隙连接,从而为它们提供电和代谢通道交流,从而在健康以及疾病中发挥信号和新陈代谢作用。只有少数研究将间隙连接作为视网膜再生或至少是神经调节的潜在靶标。它们对细胞再生的真正贡献尚未揭晓

     来自匈牙利佩奇大学医学院的Tamás Kovács-Öller团队认为作为保留大量结构和功能相似性的中枢神经系统易于访问的一部分,视网膜提供了一个很好的模型系统,可以揭示尚未发现的神经元信号传导机制以及影响神经组织的退行性疾病的潜在治疗方法。视网膜作为模型的一个主要缺点是其有限的再生能力。间隙连接特异性药理剂以及间隙连接相关的基因治疗和刺激可以成功地用于限制视网膜疾病中的退变过程。该成果可以推广至其他中枢神经系统病变的治疗

文章在《中国神经再生研究(英文版)》杂志202110 10期发表。

https://orcid.org/0000-0002-3353-4485 (Tamás Kovács-Öller); 

https://orcid.org/0000-0001-8121-2600 (Gergely Szarka); 

https://orcid.org/0000-0001-7481-390X (Béla Völgyi) 

Abstract: Vision altering diseases, such as glaucoma, diabetic retinopathy, age-related macular degeneration, myopia, retinal vascular disease, traumatic brain injuries and others cripple many lives and are projected to continue to cause anguish in the foreseeable future. Gap junctions serve as an emerging target for neuromodulation and possible regeneration as they directly connect healthy and/or diseased cells, thereby playing a crucial role in pathophysiology. Since they are permeable for macromolecules, able to cross the cellular barriers, they show duality in illness as a cause and as a therapeutic target. In this review, we take recent advancements in gap junction neuromodulation (pharmacological blockade, gene therapy, electrical and light stimulation) into account, to show the gap junction’s role in neuronal cell death and the possible routes of rescuing neuronal and glial cells in the retina succeeding illness or injury.

Key words: age-related macular degeneration, bystander effect, connexin, diabetic retinopathy, gap junction, glaucoma, neuromodulation, retina, retinal disease, vision