Influences of glaucoma on the structure and function of synapses in the visual system.
Influences of glaucoma on the structure and function of synapses in the visual system.
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DOI：
10.1089/ars.2021.0253
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发表时间：
2022-01
影响因子：
6.6
通讯作者：
M. V. Van Hook
中科院分区：
文献类型：
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作者：
M. V. Van Hook
意义 青光眼是一种与年龄相关的视觉系统神经退行性疾病，与眼压 (IOP) 敏感性相关。它是全世界视力丧失的首要不可逆原因，视力丧失是由视网膜输出神经元（称为视网膜神经节细胞（RGC））的损伤和功能障碍引起的。最新进展：眼压升高和视神经损伤会触发 RGC 树突的修剪、突触前双极细胞兴奋性输入形态的改变以及 RGC 突触功能的破坏。尽管迄今为止的证据表明青光眼与大脑中 RGC 投射目标的线粒体和突触结构和功能改变有关，但人们对 RGC 输出知之甚少。这些早期功能变化可能会导致视力丧失，并可能成为早期诊断和治疗的窗口。关键问题 青光眼在不同程度上和不同的时间过程中影响不同的 RGC 人群。青光眼对 RGC 突触功能的影响以及这些影响的机制仍有待确定。由于 RGC 是一个特别需要能量的神经元群体，线粒体的细胞内轴突运输和线粒体功能的改变可能会导致视网膜大脑中的 RGC 突触功能障碍以及青光眼中的 RGC 脆弱性。未来方向 差异 RGC 脆弱性的潜在机制仍有待确定。此外，RGC 突触功能障碍和变性的时间和机制将为了解青光眼的疾病过程提供有价值的见解。未来的工作将能够利用这些发现来更好地设计诊断和治疗方法来检测疾病和预防视力丧失。
SIGNIFICANCE Glaucoma is an age-related neurodegenerative disorder of the visual system associated with sensitivity to intraocular pressure (IOP). It is the leading irreversible cause of vision loss worldwide and vision loss results from damage and dysfunction of the retinal output neurons known as retinal ganglion cells (RGCs). Recent Advances: Elevated IOP and optic nerve injury triggers pruning of RGC dendrites, altered morphology of excitatory inputs from presynaptic bipolar cells, and disrupted RGC synaptic function. Less is known about RGC outputs, although evidence to date indicates that glaucoma is associated with altered mitochondrial and synaptic structure and function in RGC-projection targets in the brain. These early functional changes likely contribute to vision loss and might be a window into early diagnosis and treatment. CRITICAL ISSUES Glaucoma affects different RGC populations to varying extents and along distinct time courses. The influence of glaucoma on RGC synaptic function as well as the mechanisms underlying these effects remain to be determined. Since RGCs are an especially energetically-demanding population of neurons, altered intracellular axon transport of mitochondria and mitochondrial function might contribute to RGC synaptic dysfunction in the retina brain as well as RGC vulnerability in glaucoma. FUTURE DIRECTIONS The mechanisms underlying differential RGC vulnerability remain to be determined. Moreover, the timing and mechanisms of RGCs synaptic dysfunction and degeneration will provide valuable insight into the disease process in glaucoma. Future work will be able to capitalize on these findings to better design diagnostic and therapeutic approaches to detect disease and prevent vision loss.