Astrocytes of the eye and optic nerve: heterogeneous populations with unique functions mediate axonal resilience and vulnerability to glaucoma.
Astrocytes of the eye and optic nerve: heterogeneous populations with unique functions mediate axonal resilience and vulnerability to glaucoma.
复制标题
眼和视神经的星形胶质细胞：具有独特功能的异质群体调节轴突弹性和对青光眼的易感性。
DOI：
10.3389/fopht.2023.1217137
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发表时间：
2023-01-01
期刊：
影响因子：
--
通讯作者：
Sun, Daniel
中科院分区：
文献类型：
--
作者：
Cullen, Paul F;Sun, Daniel
神经胶质细胞，特别是星形胶质细胞，在中枢神经系统对损伤和神经退行性疾病的反应中的作用是一个越来越深入的研究课题。这些细胞在生理条件下执行多种支持功能，但在受到伤害(包括青光眼)时，它们会发生行为变化--统称为“反应性”--以应对神经元内稳态的破坏。然而，关于反应性如何改变疾病进展--无论是有益的还是有害的--以及这些变化是否可以通过治疗调节以改善结果，仍有许多未知之处。从历史上看，星形胶质细胞行为的异质性在生理和病理条件下都没有得到充分的解决，导致对它们对健康和疾病的贡献的认识支离破碎，往往相互矛盾。由于近年来越来越多的关注，我们现在知道这种异质性既包括生理功能的内在变化，也包括因病理而异的侮辱特异性变化。尽管之前的研究表明，在人类疾病和动物模型中，青光眼中都存在星形胶质细胞的变化，但总的来说，这些发现并不能确定星形胶质细胞与神经保护或变性的致病作用有关，而不是与随后的反应有关。通过利用大脑星形胶质细胞的知识来加强我们的理解的努力受到了文献中突触周围灰质星形胶质细胞发现的首要地位的限制，而青光眼的许多早期变性发生在由纤维状“白质”星形胶质细胞聚集的轴突区域。然而，通过关注前视觉通路的星形胶质细胞--视网膜、无髓视神经头和有髓视神经区的星形胶质细胞--我们的目标是强调它们行为中可能导致轴突脆弱性和青光眼进展的方面，包括在线粒体周转和能量供应中的作用。此外，我们假设，视网膜、视神经头和有髓视神经的星形胶质细胞，尽管有着共同的发育起源并由缝隙连接网络连接，但最好被理解为居住在明显不同的利基环境中的不同群体，并伴随着功能特化。仔细研究它们的行为特征，不仅可以阐明它们在青光眼中的作用，还可以阐明它们诱导保护性行为的机制，这些保护性行为可以阻止进行性轴突损伤和视网膜神经节细胞死亡，在这种毁灭性的条件下，视网膜神经节细胞死亡导致视力丧失。
The role of glia, particularly astrocytes, in mediating the central nervous system's response to injury and neurodegenerative disease is an increasingly well studied topic. These cells perform myriad support functions under physiological conditions but undergo behavioral changes - collectively referred to as 'reactivity' - in response to the disruption of neuronal homeostasis from insults, including glaucoma. However, much remains unknown about how reactivity alters disease progression - both beneficially and detrimentally - and whether these changes can be therapeutically modulated to improve outcomes. Historically, the heterogeneity of astrocyte behavior has been insufficiently addressed under both physiological and pathological conditions, resulting in a fragmented and often contradictory understanding of their contributions to health and disease. Thanks to increased focus in recent years, we now know this heterogeneity encompasses both intrinsic variation in physiological function and insult-specific changes that vary between pathologies. Although previous studies demonstrate astrocytic alterations in glaucoma, both in human disease and animal models, generally these findings do not conclusively link astrocytes to causative roles in neuroprotection or degeneration, rather than a subsequent response. Efforts to bolster our understanding by drawing on knowledge of brain astrocytes has been constrained by the primacy in the literature of findings from peri-synaptic 'gray matter' astrocytes, whereas much early degeneration in glaucoma occurs in axonal regions populated by fibrous 'white matter' astrocytes. However, by focusing on findings from astrocytes of the anterior visual pathway - those of the retina, unmyelinated optic nerve head, and myelinated optic nerve regions - we aim to highlight aspects of their behavior that may contribute to axonal vulnerability and glaucoma progression, including roles in mitochondrial turnover and energy provisioning. Furthermore, we posit that astrocytes of the retina, optic nerve head and myelinated optic nerve, although sharing developmental origins and linked by a network of gap junctions, may be best understood as distinct populations residing in markedly different niches with accompanying functional specializations. A closer investigation of their behavioral repertoires may elucidate not only their role in glaucoma, but also mechanisms to induce protective behaviors that can impede the progressive axonal damage and retinal ganglion cell death that drive vision loss in this devastating condition.