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IOP and glaucoma damage: The essential role of optic nerve head and retinal mechanosensors
Progress in Retinal and Eye Research ( IF 17.8 ) Pub Date : 2023-12-16 , DOI: 10.1016/j.preteyeres.2023.101232
Ian Pitha , Liya Du , Thao Nguyen , Harry Quigley

There are many unanswered questions on the relation of intraocular pressure to glaucoma development and progression. IOP itself cannot be distilled to a single, unifying value, because IOP level varies over time, differs depending on ocular location, and can be affected by method of measurement. Ultimately, IOP level creates mechanical strain that affects axonal function at the optic nerve head which causes local extracellular matrix remodeling and retinal ganglion cell death – hallmarks of glaucoma and the cause of glaucomatous vision loss. Extracellular tissue strain at the ONH and lamina cribrosa is regionally variable and differs in magnitude and location between healthy and glaucomatous eyes. The ultimate targets of IOP-induced tissue strain in glaucoma are retinal ganglion cell axons at the optic nerve head and the cells that support axonal function (astrocytes, the neurovascular unit, microglia, and fibroblasts). These cells sense tissue strain through a series of signals that originate at the cell membrane and alter cytoskeletal organization, migration, differentiation, gene transcription, and proliferation. The proteins that translate mechanical stimuli into molecular signals act as band-pass filters – sensing some stimuli while ignoring others – and cellular responses to stimuli can differ based on cell type and differentiation state. Therefore, to fully understand the IOP signals that are relevant to glaucoma, it is necessary to understand the ultimate cellular targets of IOP-induced mechanical stimuli and their ability to sense, ignore, and translate these signals into cellular actions.

中文翻译:

眼压和青光眼损伤:视神经乳头和视网膜机械传感器的重要作用

关于眼压与青光眼发生和进展的关系还有许多未解答的问题。IOP 本身无法提取为单一的统一值,因为 IOP 水平随时间变化、根据眼睛位置而变化,并且可能受到测量方法的影响。最终,眼压水平会产生机械应变,影响视神经乳头的轴突功能,导致局部细胞外基质重塑和视网膜神经节细胞死亡——青光眼的标志和青光眼视力丧失的原因。ONH 和筛板的细胞外组织应变具有区域性差异,并且健康眼睛和青光眼眼睛之间的大小和位置不同。青光眼中 IOP 诱导的组织应变的最终目标是视神经乳头的视网膜神经节细胞轴突和支持轴突功能的细胞(星形胶质细胞、神经血管单元、小胶质细胞和成纤维细胞)。这些细胞通过一系列源自细胞膜的信号感知组织应变,并改变细胞骨架组织、迁移、分化、基因转录和增殖。将机械刺激转化为分子信号的蛋白质充当带通滤波器——感知一些刺激而忽略其他刺激——细胞对刺激的反应可能因细胞类型和分化状态而异。因此,为了充分了解与青光眼相关的 IOP 信号,有必要了解 IOP 诱导的机械刺激的最终细胞目标及其感知、忽略这些信号并将其转化为细胞行为的能力。
更新日期:2023-12-16
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