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Editors Selection IGR 9-4

Basic Research - RGC: Cyclical shear stress

Comment by Arthur Sit on:

46708 Are intracranial pressure fluctuations important in glaucoma?, Wostyn P; De Groot V; Audenaert K et al., Medical Hypotheses, 2011;

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The role of intracranial pressure (ICP) in glaucoma pathogenesis has generated significant interest since Berdahl et al.^1,2 reported clinical evidence indicating an association between glaucoma and low CSF pressure. Ren et al.³ confirmed these relationships in a prospective study demonstrating that the CSF pressure was significantly higher in a control group than either high pressure or normal pressure glaucoma patients. As well, the trans-lamina cribrosa pressure was significantly lower in the control group than either glaucoma group. The mechanisms most commonly proposed to explain the contribution of ICP to glaucoma are direct strain on the lamina cribrosa from the translaminar pressure difference, and the inhibition of retrograde axoplasmic flow due to a high translaminar pressure gradient. Wostyn et al. (1664) proposed ICP fluctuations a potentially exacerbating factor to high translaminar pressure. They reviewed evidence indicating that cyclical shear stress may be more damaging to neurons than an equal, but steady, shear stress. Two in-vitro studies using neuron-like cells demonstrated an increased strain-rate, and increased increased DNA fragmentation with cyclical stress compared with steady stress.^4,5 Wostyn et al. Also reviewed the evidence for the existence of ICP fluctuations, citing evidence from continuous ICP monitoring in normal pressure hydrocephalus patients. Fluctuations in ICP could result in fluctuations of the translaminar pressure, and thus fluctuations in the shear stress in the retinal ganglion cell axons. However, whether or not similar ICP fluctuations occur in glaucoma patients is unknown. Nevertheless, the hypothesis that ICP fluctuations may contribute to glaucoma pathogenesis adds another potential risk factor that needs to be considered. There is a clear theoretical basis for the role of translaminar cribrosa pressure gradients in glaucoma, and the authors have reviewed in-vitro evidence suggesting a pathogenic role for fluctuations in the pressure gradient. Whether or not ICP and IOP fluctuations occur in phase, essentially cancelling each other out, or out of phase, potentially exacerbating the translaminar pressure gradient, is unknown. As well, the fluctuation of ocular perfusion pressure (OPP) should be considered since it may be affected by similar factors, such as changes in body position. Further work is clearly needed to understand the role of ICP fluctuations in glaucoma, and its interaction with IOP and OPP fluctuations.

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