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Computational study of the mechanical behavior of the astrocyte network and axonal compartments in the mouse optic nerve head

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Abstract

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.

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Data and results generated from this study are presented in detail in the supplemental materials.

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Acknowledgements

This work was supported by the National Institutes of Health EY 02120 (HQ); EY 01765 (Core facility grant, Wilmer Eye Institute); unrestricted donations to the Glaucoma Center of Excellence, Wilmer Eye Institute; the National Science Foundation Award 1727104 (TDN); Brightfocus Foundation G2015132 (TDN); and the Croucher Foundation (YTTL).

Funding

This work was supported by the National Institutes of Health EY 02120 (HQ); EY 01765 (Core facility grant, Wilmer Eye Institute); unrestricted donations to the Glaucoma Center of Excellence, Wilmer Eye Institute; the National Science Foundation Award 1727104 (TN); Brightfocus Foundation G2015132 (TN); and the Croucher Foundation (YTTL).

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Authors and Affiliations

  1. Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, USA

    Yik Tung Tracy Ling & Thao D. Nguyen

  2. Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Arina Korneva, Harry A. Quigley & Thao D. Nguyen

  3. Glaucoma Center of Excellence, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Arina Korneva & Harry A. Quigley

  4. Department of Materials Science, Johns Hopkins University, Baltimore, MD, USA

    Thao D. Nguyen

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  1. Yik Tung Tracy Ling
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YTTL and TDN wrote the main manuscript text, and YTTL prepared all the figures. All authors provided feedback on the methods, and reviewed and edited the manuscript.

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Correspondence to Thao D. Nguyen.

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Ling, Y.T.T., Korneva, A., Quigley, H.A. et al. Computational study of the mechanical behavior of the astrocyte network and axonal compartments in the mouse optic nerve head. Biomech Model Mechanobiol 22, 1751–1772 (2023). https://doi.org/10.1007/s10237-023-01752-z

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