Intracellular Flow in Optic Nerve Axons: A Mechanism for Cell Death in Glaucoma
Intracellular Flow in Optic Nerve Axons: A Mechanism for Cell Death in Glaucoma
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DOI：
10.1167/iovs.08-2396
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发表时间：
2009-08-01
影响因子：
4.4
通讯作者：
Foss, Alexander J. E.
中科院分区：
文献类型：
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作者：
Band, Leah R.;Hall, Cameron L.;Foss, Alexander J. E.
目的.在青光眼中，升高的眼内压引起视网膜神经节细胞的进行性丧失并导致视神经病变。作者提出了一种细胞死亡的潜在机制，即眼内压升高导致液体渗透轴突膜，在轴突内产生被动的细胞内液体流动。据推测，这种细胞内流动局部消耗三磷酸腺苷（ATP）浓度，破坏轴突运输，导致细胞死亡。一个数学模型的开发，考虑到生物力学原则的基础上提出的假设，并解决了确定的机制的影响。该模型表明，青光眼中存在的升高的眼内压足以产生显著的细胞内液流动。在视神经乳头周围，这种流动可能足以破坏ATP的扩散，从而中断主动轴突运输。该数学模型表明，它是物理上合理的，一个被动的细胞内液流可以显着有助于青光眼视网膜神经节细胞轴突的病理生理。（Invest Ophthalmol维斯科学。2009; 50：3750-3758）DOI：10.1167/iovs.08-2396
PURPOSE. In glaucoma, elevated intraocular pressure causes a progressive loss of retinal ganglion cells and results in optic neuropathy. The authors propose a potential mechanism for cell death, whereby elevated intraocular pressure causes fluid to permeate axonal membranes, creating a passive intracellular fluid flow within the axons. It is hypothesized that this intracellular flow locally depletes the adenosine triphosphate (ATP) concentration, disrupting axonal transport and leading to cell death.METHODS. A mathematical model was developed that takes into account the biomechanical principles underpinning the proposed hypothesis, and was solved to determine the implications of the mechanism.RESULTS. The model suggests that the raised intraocular pressures present in glaucoma are adequate to produce significant intracellular fluid flow. In the periphery of the optic nerve head, this flow may be sufficient to disrupt the diffusion of ATP and hence interrupt active axonal transport.CONCLUSIONS. The mathematical model demonstrates that it is physically plausible that a passive intracellular fluid flow could significantly contribute to the pathophysiology of the retinal ganglion cell axon in glaucoma. (Invest Ophthalmol Vis Sci. 2009; 50: 3750-3758) DOI: 10.1167/iovs.08-2396