Sigma-1受体对视网膜神经节细胞保护机制的研究进展

Advances in neuroprotection of Sigma-1 receptor in retinal ganglion cell

摘要:

视神经病变是一类以视网膜神经节细胞(retinal ganglion cells，RGC)及轴突受损为主要特征的致盲性疾病，发病机制复杂且治疗手段有限。Sigma-1受体(Sigma-1 receptor，S1R)是一种内质网上的分子伴侣蛋白，视网膜中含量丰富，其中高表达于神经节细胞层。近年来，S1R作为神经退行性疾病的治疗靶点备受关注。越来越多研究表明S1R参与调节多种细胞功能，包括Ca²⁺稳态、内质网应激反应、氧化应激反应、神经营养因子分泌和胶质细胞活化等，在神经退行性疾病中发挥神经保护作用。视觉系统中，研究发现激动S1R同样具有保护作用，可明显改善RGC丢失及功能减低，部分逆转损伤，维持结构完整； 相反S1R缺陷则会恶化疾病进展或提高退行性疾病易感性。本文综述了S1R对视网膜中RGC的保护作用及其机制的研究进展，旨在深入了解其功能及机制，为视神经病变治疗提供新靶点。

Abstract:

With complicated pathogenesis and limited treatment options, optic neuropathy is one of the major blinding diseases characterized by damaged retinal ganglion cells(RGC)and axons. Sigma-1 receptor(S1R)is a chaperone protein mainly located in the endoplasmic reticulum membrane, which is abundant in retina and highly expressed in the ganglion cell layer. S1R has been noted increasingly as a novel target for the treatment of neuro-degenerations. More studies have shown that S1R is a pluripotent modulator including Ca²⁺ homeostasis, endoplasmic reticulum stress response, oxidative stress response, neurotrophic factor secretion and glial cell activation, indicating that S1R can generate significant impacts on neuroprotection in neurodegenerative diseases. Additionally, S1R also has neuroprotective effects against RGC loss and dysfunction both in vivo and in vitro, reversing loss partially and maintaining structural integrity, while the absence of S1R exacerbates the disease or increases vulnerability to degenerative diseases. This article intends to review the progress and mechanisms in neuroprotection of S1R in RGC, aiming to provide a new target for the treatment of optic neuropathy.