Myelin Distribution at the Optic Nerve Myelination Transition Zone Influences Axonal Biomechanics

2026-08-07

AI Summary

This study investigates the potential role of mechanical discontinuity at the myelination transition zone (MTZ) of the optic nerve in early glaucomatous damage. By developing a multiscale finite element model that integrates the macroscopic globe with the microscopic lamina cribrosa–axon architecture, the work quantifies, for the first time, how different MTZ boundary configurations influence axonal biomechanical responses under intraocular pressures of 15 and 45 mmHg. The results demonstrate that the unmyelinated region endures substantially higher mechanical loads, and posterior displacement of the MTZ markedly exacerbates stress and strain discontinuities across the interface. These findings highlight MTZ geometry as a critical determinant of the local mechanical microenvironment surrounding axons, offering a novel biomechanical perspective on the pathogenesis of glaucoma.

Abstract

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.

Problem

• myelination transition zone
• axonal biomechanics
• glaucoma
• retinal ganglion cell
• lamina cribrosa

Innovation

• multiscale finite element modeling
• myelination transition zone
• axonal biomechanics
• lamina cribrosa
• mechanical discontinuity