视神经髓鞘化过渡区的髓鞘分布影响轴突生物力学
Myelin Distribution at the Optic Nerve Myelination Transition Zone Influences Axonal Biomechanics
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中文总结 AI 辅助
本研究通过多尺度有限元框架发现，视神经髓鞘化过渡区的髓鞘分布构型会影响轴突生物力学，且其偏移量越大，髓鞘边界处的机械不连续性越显著，为青光眼损伤机制研究提供了新视角。
中文摘要 AI 辅助
目的：筛板（LC）被认为是青光眼性视网膜神经节细胞（RGC）损伤的初始部位，也是无髓鞘RGC轴突发生髓鞘化的区域。本研究试图使用有限元（FE）模型，探究髓鞘化过渡区（MTZ）的构型如何影响RGC轴突受到的机械损伤。方法：开发了一种多尺度有限元框架，以探究髓鞘分布对眼压（IOP）诱导的MTZ处轴突应力和应变的生物力学效应。采用基于解剖结构的宏观有限元眼模型，计算15 mmHg和45 mmHg眼压下的筛板变形，随后将这些变形应用于后筛板的微观模型，该模型包含轴突、髓鞘和周围基质。模拟了四种不同的MTZ边界构型：一种平坦构型和三种具有3、6或9 μm随机后偏移的构型，代表潜在的生理变异。量化了不同MTZ构型下眼压诱导的有效轴突应变和应力。结果：在眼压负荷下，轴突表现出纵向压缩和横向拉伸，且在髓鞘边界处存在明显的有效应力和应变不连续性。在所有模型中，无髓鞘区域的有效应力和应变均高于有髓鞘区域，且这种机械不连续性随MTZ偏移量增大而增加。结论：此前已有研究提出青光眼相关的髓鞘脱失早于视网膜神经纤维层（RNFL）变薄，本研究表明MTZ构型直接影响RGC轴突的生物力学。不同MTZ轮廓是否会引发青光眼性损伤、髓鞘脱失是否会加速疾病进展，或两种机制是否共同起作用，仍有待确定。
英文摘要
Purpose: The lamina cribrosa (LC) is considered the initial site of glaucomatous retinal ganglion cell (RGC) injury, and is also the region where unmyelinated RGC axons become myelinated. Here we sought to use finite element (FE) modeling to investigate how the configuration of the myelination transition zone (MTZ) influences the mechanical insult to RGC axons. Methods: A multiscale FE framework was developed to investigate the biomechanical effect of myelin distribution on IOP-induced axonal stress and strain at the MTZ. An anatomically based macro-scale FE eye model was used to compute LC deformations under 15 and 45 mmHg IOP. These deformations were then applied to micro-scale models of the posterior LC, consisting of axons, myelin sheaths, and surrounding matrix. Four distinct MTZ boundary configurations were simulated: one flat and three with random posterior offsets of 3, 6, or 9 μm, representing potential physiological variations. IOP-induced effective axonal strains and stresses were quantified across the different MTZ configurations. Results: Under IOP loading, axons exhibited longitudinal compression and transverse stretch, with marked effective stress and strain discontinuities at the myelin boundary. Across all models, the unmyelinated region exhibited higher effective stress and strain than the myelinated region, and this mechanical discontinuity increased with larger MTZ offsets. Conclusions: Glaucoma-associated demyelination has been previously suggested to precede RNFL thinning. Here we have shown that the MTZ configuration directly influences RGC axonal mechanics. Whether different MTZ profiles can initiate glaucomatous injury, whether demyelination accelerates disease progression, or whether both mechanisms contribute, remains to be determined.
