Effects of collagen microstructure and material properties on the deformation of the neural tissues of the lamina cribrosa

Voorhees, Andrew; Jan, N.-J.; Sigal, Ian A.

doi:10.1016/j.actbio.2017.05.042

Cited by 52 publications

(57 citation statements)

References 44 publications

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“…4 – 8 The exact mechanisms linking IOP to axonal damage have not been fully delineated, but the translation of IOP into mechanical stress at the ONH has been extensively studied and modeled. 9 – 11 An increase in the IOP is postulated to produce trans-LC axial stress and circumferential hoop stress on the LC. Astrocytes bridge the mouse ONH and are anchored by peripheral processes to the peripapillary sclera.…”

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confidence: 99%

Pressure-Induced Changes in Astrocyte GFAP, Actin, and Nuclear Morphology in Mouse Optic Nerve

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Jefferys

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Purpose To conduct quantitative analysis of astrocytic glial fibrillary acidic protein (GFAP), actin and nuclei distribution in mouse optic nerve (ON) and investigate changes in the measured features after 3 days of ocular hypertension (OHT). Method Serial cross-sections of 3-day microbead-induced OHT and control ONs were fluorescently labelled and imaged using confocal microscope. Eighteen structural features were measured from the acquired images, including GFAP coverage, actin area fraction, process thickness, and aspect ratio of cell nucleus. The measured features were analyzed for variations with axial locations along ON and radial zones transverse to ON, as well as for the correlations with degree of intraocular pressure (IOP) change. Results The most significant changes in structural features after 3-day OHT occurred in the unmyelinated ON region (R1), and the changes were greater with greater IOP elevation. Although the GFAP, actin, axonal, and ON areas all increased in 3-day OHT ONs in R1 ( P ≤ 0.004 for all), the area fraction of GFAP actually decreased ( P = 0.02), the actin area fraction was stable and individual axon compartments were unchanged in size. Within R1, the number of nuclear clusters increased ( P < 0.001), but the mean size of nuclear clusters was smaller ( P = 0.02) and the clusters became rounder ( P < 0.001). In all cross-sections of control ONs, astrocytic processes were thickest in the rim zone compared with the central and peripheral zones ( P ≤ 0.002 for both), whereas the overall process width in R1 decreased after 3 days of OHT ( P < 0.001). Conclusions The changes in structure elucidated IOP-generated alterations that underlie astrocyte mechanotranslational responses relevant to glaucoma.

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confidence: 99%

Pressure-Induced Changes in Astrocyte GFAP, Actin, and Nuclear Morphology in Mouse Optic Nerve

Ling

Pease

Jefferys

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…Following the approaches used elsewhere to study the mechanical effects of PPS collagen fiber architecture [23, 29, 30], we modeled the ONH as a disk (Fig. 2).…”

Section: Methodsmentioning

confidence: 99%

“…This pressure was calculated based on the law of Laplace for a thin walled-sphere, with a hoop stress multiplier (one half the ratio of the sphere radius to the wall thickness) equal to 10 as in our previous studies. [29, 30] This loading created a state of in-plane biaxial tensile stress in the ONH. Readers interested in more details on the usage, assumptions, and limitations of the law of Laplace are directed to our previous work.…”

Section: Methodsmentioning

confidence: 99%

Peripapillary sclera architecture revisited: A tangential fiber model and its biomechanical implications

et al. 2018

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It is hypothesized that vision loss in glaucoma is due to excessive mechanical deformation within the neural tissue inside the scleral canal. This study proposes a new model for how the collagen of the peripapillary sclera surrounding the canal is organized to support the delicate neural tissue inside. Previous low-resolution studies of the peripapillary sclera suggested that the collagen fibers are arranged in a ring around the canal. Instead, we provide microscopic evidence suggesting that the canal is also supported by long-running interwoven fibers oriented tangentially to the canal. We demonstrate that this arrangement has multiple biomechanical advantages over a circular collagen arrangement and can explain previously unexplained experimental findings including contraction of the scleral canal under elevated intraocular pressure.

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“…We have recently developed and reported on microstructure-specific models based on high-resolution polarized light images that allows us to distinguish between the load-bearing, stiff, laminar beams and the frail, compliant, neural tissues of the LC. 32 The goal of this study was to leverage these microstructure-based models to determine if the shape and size of LC pores predicts the biomechanical insult within the neural tissues of the pores due to IOP-induced hoop stress.…”

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confidence: 99%

Lamina Cribrosa Pore Shape and Size as Predictors of Neural Tissue Mechanical Insult

Voorhees

Jan

Austin

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeThe purpose of this study was to determine how the architecture of the lamina cribrosa (LC) microstructure, including the shape and size of the lamina pores, influences the IOP-induced deformation of the neural tissues within the LC pores using computational modeling.MethodsWe built seven specimen-specific finite element models of LC microstructure with distinct nonlinear anisotropic properties for LC beams and neural tissues based on histological sections from three sheep eyes. Changes in shape (aspect ratio and convexity) and size (area and perimeter length) due to IOP-induced hoop stress were calculated for 128 LC pores. Multivariate linear regression was used to determine if pore shape and size were correlated with the strain in the pores. We also compared the microstructure models to a homogenized model built following previous approaches.ResultsThe LC microstructure resulted in focal tensile, compressive, and shear strains in the neural tissues of the LC that were not predicted by homogenized models. IOP-induced hoop stress caused pores to become larger and more convex; however, pore aspect ratio did not change consistently. Peak tensile strains within the pores were well predicted by a linear regression model considering the initial convexity (negative correlation, P < 0.001), aspect ratio (positive correlation, P < 0.01), and area (negative correlation, P < 0.01). Significant correlations were also found when considering the deformed shape and size of the LC pores.ConclusionsThe deformation of the LC neural tissues was largely dependent on the collagenous LC beams. Simple measures of LC pore shape and area provided good estimates of neural tissue biomechanical insult.

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Effects of collagen microstructure and material properties on the deformation of the neural tissues of the lamina cribrosa

Cited by 52 publications

References 44 publications

Pressure-Induced Changes in Astrocyte GFAP, Actin, and Nuclear Morphology in Mouse Optic Nerve

Pressure-Induced Changes in Astrocyte GFAP, Actin, and Nuclear Morphology in Mouse Optic Nerve

Peripapillary sclera architecture revisited: A tangential fiber model and its biomechanical implications

Lamina Cribrosa Pore Shape and Size as Predictors of Neural Tissue Mechanical Insult

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