Glaucoma is a blinding disease characterized by the degeneration of the retinal ganglion cell (RGC) axons at the optic nerve head (ONH). A major risk factor for glaucoma is the intraocular pressure (IOP). However, it is currently impossible to measure the IOP-induced mechanical response of the axons of the ONH. The objective of this study was to develop a computational modeling method to estimate the IOP-induced strains and stresses in the axonal compartments in the mouse astrocytic lamina (AL) of the ONH, and to investigate the effect of the structural features on the mechanical behavior. We developed experimentally informed finite element (FE) models of six mouse ALs to investigate the effect of structure on the strain responses of the astrocyte network and axonal compartments to pressure elevation. The specimen-specific geometries of the FE models were reconstructed from confocal fluorescent images of cryosections of the mouse AL acquired in a previous study that measured the structural features of the astrocytic processes and axonal compartments. The displacement fields obtained from digital volume correlation in prior inflation tests of the mouse AL were used to determine the displacement boundary conditions of the FE models. We then applied Gaussian process regression to analyze the effects of the structural features on the strain outcomes simulated for the axonal compartments. The axonal compartments experienced, on average, 6 times higher maximum principal strain but 1800 times lower maximum principal stress compared to those experienced by the astrocyte processes. The strains experienced by the axonal compartments were most sensitive to variations in the area of the axonal compartments. Larger axonal compartments that were more vertically aligned, closer to the AL center, and with lower local actin area fraction had higher strains. Understanding the factors affecting the deformation in the axonal compartments will provide insights into mechanisms of glaucomatous axonal damage.

青光眼是一种致盲性疾病，其特征是视神经乳头 (ONH) 的视网膜神经节细胞 (RGC) 轴突退化。青光眼的一个主要危险因素是眼压（IOP）。然而，目前不可能测量 IOP 引起的 ONH 轴突的机械响应。本研究的目的是开发一种计算建模方法来估计 IOP 诱导的 ONH 星形细胞层 (AL) 轴突室中的应变和应力，并研究结构特征对机械行为的影响。我们开发了六种小鼠 AL 的实验有限元 (FE) 模型，以研究结构对星形胶质细胞网络和轴突室对压力升高的应变反应的影响。有限元模型的样本特定几何形状是根据先前研究中获得的小鼠 AL 冷冻切片的共焦荧光图像重建的，该研究测量了星形胶质细胞过程和轴突室的结构特征。在先前的小鼠 AL 充气测试中通过数字体积相关获得的位移场用于确定有限元模型的位移边界条件。然后，我们应用高斯过程回归来分析结构特征对轴突室模拟应变结果的影响。与星形胶质细胞突起相比，轴突室平均承受的最大主应变高 6 倍，但最大主应力低 1800 倍。轴突室所经历的应变对轴突室面积的变化最敏感。 较大的轴突区室更垂直对齐、更靠近 AL 中心、局部肌动蛋白面积分数较低，具有较高的应变。了解影响轴突室变形的因素将有助于深入了解青光眼轴突损伤的机制。