The heterogeneity of astrocytes in glaucoma.

The heterogeneity of astrocytes in glaucoma.
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青光眼中星形胶质细胞的异质性

DOI:
10.3389/fnana.2022.995369
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发表时间:
2022
影响因子:
2.9
通讯作者:
--
中科院分区:
医学3区
文献类型:
--
作者:

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青光眼是视网膜神经节细胞进行性变性导致失明的主要原因。衰老和眼内压(IOP)升高是主要的风险因素。降低IOP并不总是阻止疾病进展。保护视神经的替代方法在青光眼中得到了深入研究。星形胶质细胞是存在于视网膜、视神经乳头(optic nerve head,ONH)和视脑中的大胶质细胞,维持神经元的稳态,调节神经元的活动,是对视网膜和脑损伤的免疫反应的一部分。在这篇简短的综述中,我们讨论了青光眼患者和动物模型的视网膜、视神经乳头和视脑中星形胶质细胞的激活和异质性。我们还讨论了最近的一些转基因和基因敲除研究青光眼小鼠模型,以澄清星形胶质细胞在青光眼发病机制中的作用。星形胶质细胞是一种异质性细胞,在青光眼的发病机制中起着至关重要的作用,特别是在神经炎症和线粒体功能障碍的过程中。在星形胶质细胞中,过表达Stat 3或敲低IκKβ/p65、caspase-8和线粒体解偶联蛋白(Ucp 2)可减少青光眼小鼠模型中的神经节细胞丢失。基于这些研究,通过增强其有益反应性或抑制其有害反应性来靶向反应性星形胶质细胞的异质性的治疗策略是未来青光眼治疗的替代选择。
Glaucoma is a leading cause of blindness with progressive degeneration of retinal ganglion cells. Aging and increased intraocular pressure (IOP) are major risk factors. Lowering IOP does not always stop the disease progression. Alternative ways of protecting the optic nerve are intensively studied in glaucoma. Astrocytes are macroglia residing in the retina, optic nerve head (ONH), and visual brain, which keep neuronal homeostasis, regulate neuronal activities and are part of the immune responses to the retina and brain insults. In this brief review, we discuss the activation and heterogeneity of astrocytes in the retina, optic nerve head, and visual brain of glaucoma patients and animal models. We also discuss some recent transgenic and gene knockout studies using glaucoma mouse models to clarify the role of astrocytes in the pathogenesis of glaucoma. Astrocytes are heterogeneous and play crucial roles in the pathogenesis of glaucoma, especially in the process of neuroinflammation and mitochondrial dysfunction. In astrocytes, overexpression of Stat3 or knockdown of IκKβ/p65, caspase-8, and mitochondrial uncoupling proteins (Ucp2) can reduce ganglion cell loss in glaucoma mouse models. Based on these studies, therapeutic strategies targeting the heterogeneity of reactive astrocytes by enhancing their beneficial reactivity or suppressing their detrimental reactivity are alternative options for glaucoma treatment in the future.
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