Department of Bioengineering, Imperial College London, London, United Kingdom.
Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology & Emory University School of Medicine, Atlanta, Georgia, United States.
Invest Ophthalmol Vis Sci. 2024 Jun 3;65(6):4. doi: 10.1167/iovs.65.6.4.
Shear-induced nitric oxide (NO) production by Schlemm's canal (SC) endothelial cells provides a fast, IOP-sensitive feedback signal that normally contributes to IOP homeostasis. Our goal was to analyze the response of this homeostatic system under constant flow perfusion (as occurs in vivo) vs. constant pressure perfusion (as typical for laboratory perfusions).
A mathematical model of aqueous humor dynamics, including shear-mediated NO signaling, was formulated and analyzed for stability. The model includes Goldmann's equation, accounting for proximal and distal outflow resistance, and describes how elevated IOP causes narrowing of SC lumen that increases the shear stress on SC cells. Elevated shear stress stimulates NO production, which acts to reduce outflow resistance and relax trabecular meshwork cells to decrease trabecular meshwork stiffness, affecting the SC luminal caliber.
During constant flow perfusion, the outflow system is typically stable, returning to baseline IOP after a perturbation. In contrast, during constant pressure perfusion, the outflow system can become unstable and exhibit a time-dependent change in outflow resistance that diverges from baseline.
The stability of shear mediated IOP homeostasis is predicted to differ critically between constant flow vs. constant pressure perfusion. Because outflow facility is typically measured at a constant pressure in the laboratory, this instability may contribute to the characteristic time-dependent increase in outflow facility, known as washout, observed in many nonhuman species. Studies of IOP homeostasis should consider how the outflow system may respond differently under constant pressure vs. constant flow perfusion.
施莱姆氏管（SC）内皮细胞产生的剪切诱导型一氧化氮（NO）提供了一个快速、眼压敏感的反馈信号，通常有助于眼压的动态平衡。我们的目标是分析在恒流灌注（如体内发生的情况）与恒压灌注（如实验室灌注的典型情况）下这种动态平衡系统的反应。
建立了一个包括剪切介导的 NO 信号在内的房水动力学数学模型，并对其稳定性进行了分析。该模型包括 Goldmann 方程，考虑了近端和远端流出阻力，并描述了升高的眼压如何导致 SC 管腔变窄，从而增加 SC 细胞的剪切应力。升高的剪切应力刺激 NO 的产生，这有助于降低流出阻力，使小梁网细胞松弛，从而降低小梁网硬度，影响 SC 管腔口径。
在恒流灌注期间，流出系统通常是稳定的，在受到干扰后会恢复到基础眼压。相比之下，在恒压灌注期间，流出系统可能变得不稳定，并表现出与基础眼压偏离的流出阻力的时变变化。
剪切介导的眼压动态平衡的稳定性预计在恒流与恒压灌注之间会有很大的差异。由于在实验室中通常以恒压测量流出能力，这种不稳定性可能导致许多非人类物种中观察到的特征性的流出能力随时间增加（称为洗脱）。眼压动态平衡的研究应考虑流出系统在恒压与恒流灌注下可能会有不同的反应。
