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

ABSTRACT: It is widely considered that intraocular pressure (IOP)-induced deformation within the neural tissue pores of the lamina cribrosa (LC) contributes to neurodegeneration and glaucoma. Our goal was to study how the LC microstructure and mechanical properties determine the mechanical insult to the neural tissues within the pores of the LC. Polarized light microscopy was used to measure the collagen density and orientation in histology sections of three sheep optic nerve heads (ONH) at both mesoscale (4.4?m) and microscale (0.73?m) resolutions. Mesoscale fiber-aware FE models were first used to calculate ONH deformations at an IOP of 30mmHg. The results were then used as boundary conditions for microscale models of LC regions. Models predicted large insult to the LC neural tissues, with 95th percentile 1st principal strains ranging from 7 to 12%. Pores near the scleral boundary suffered significantly higher stretch compared to pores in more central regions (10.0±1.4% vs. 7.2±0.4%; p=0.014; mean±SD). Variations in material properties altered the minimum, median, and maximum levels of neural tissue insult but largely did not alter the patterns of pore-to-pore variation, suggesting these patterns are determined by the underlying structure and geometry of the LC beams and pores. To the best of our knowledge, this is the first computational model that reproduces the highly heterogeneous neural tissue strain fields observed experimentally. STATEMENT OF SIGNIFICANCE:The loss of visual function associated with glaucoma has been attributed to sustained mechanical insult to the neural tissues of the lamina cribrosa due to elevated intraocular pressure. Our study is the first computational model built from specimen-specific tissue microstructure to consider the mechanics of the neural tissues of the lamina separately from the connective tissue. We found that the deformation of the neural tissue was much larger than that predicted by any recent microstructure-aware models of the lamina. These results are consistent with recent experimental data and the highest deformations were found in the region of the lamina where glaucomatous damage first occurs. This study provides new insight into the complex biomechanical environment within the lamina.

SUBMITTER: Voorhees AP

PROVIDER: S-EPMC5537032 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Voorhees A P AP Jan N-J NJ Sigal I A IA

Acta biomaterialia 20170518

It is widely considered that intraocular pressure (IOP)-induced deformation within the neural tissue pores of the lamina cribrosa (LC) contributes to neurodegeneration and glaucoma. Our goal was to study how the LC microstructure and mechanical properties determine the mechanical insult to the neural tissues within the pores of the LC. Polarized light microscopy was used to measure the collagen density and orientation in histology sections of three sheep optic nerve heads (ONH) at both mesoscale ...[more]

PMID: 28528864

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Project description:Glaucoma is among the leading causes of blindness worldwide that is characterized by irreversible damage to the retinal ganglion cell axons in the lamina cribrosa (LC) region of the optic nerve head (ONH), most often associated with elevated intraocular pressure (IOP). The LC is a porous, connective tissue structure that provides mechanical support to the axons as they exit the eye and the biomechanics of the LC microstructure likely play a crucial role in protecting the axons passing through it. There is a limited knowledge of the IOP-driven biomechanics of the LC microstructure, primarily due to its small size and the difficulty with imaging the LC both in vitro and in vivo. We present finite element (FE) models of three human eye posterior poles that include the LC microstructure and interspersed neural tissues (NT) composed of retinal axons that are constructed directly from segmented, binary images of the LC. These models were used to estimate the stresses and strains in the LC and NT for an acute IOP elevation from 0 to 45 mmHg and compared with identical models except that the LC was represented as a homogenized continuum material with either homogeneous isotropic neo-Hookean properties or heterogeneous properties derived from local connective tissue volume fraction (CTVF) and predominant LC beam orientation. Stresses and strains in the LC and NT microstructure were investigated, and results were compared against those from the models wherein the LC was represented as a homogenized continuum. The regionalized volumetric average stresses and strains showed that the microstructural model yielded similar patterns to our prior approach using an LC continuum representation with mapped LC CTVF/anisotropy, but the microstructural modeling approach allows analysis of the stresses and strains in the LC and NT separately. As expected, the LC beams carried most of the IOP load in the microstructural models but exhibited less strain, while the encapsulated NT exhibited lower stresses and much higher strains. Results also revealed that the continuum models underestimate the maximum strains in the LC beams and NT by a factor of 2-3. Microstructural modeling should provide greater insight into the biomechanical factors driving damage to the axons (NT) and LC connective tissue remodeling that occur in glaucoma. The methods presented are ideal for modeling any structure with a complex microstructure composed of different materials, such as trabecular bone, lung, and tissue engineering scaffolds such as decellularized LC. Matlab code for mesh generation from a segmented image stack of the microstructure is included as Supplemental Material. STATEMENT OF SIGNIFICANCE: Glaucoma is among the leading causes of blindness worldwide that is characterized by axon damage in the lamina cribrosa (LC) region of the eye. We present a new approach for finite element modeling the entire eye-specific 3D LC microstructure and the interspersed neural tissues, incorporated into an eye-specific posterior eye model that provides appropriate boundary and loading conditions. Results are presented for three human donor eyes, showing that prior modeling approaches underestimate the stresses and strains in the laminar microstructure. We constructed models from image stacks of the segmented microstructure (Matlab code included) using an approach that is ideal for modeling any structure with a complex microstructure composed of different materials, such as trabecular bone, lung, and tissue engineering scaffolds.

Project description:The objective of this study was to measure the pressure-induced deformation response of the human lamina cribrosa (LC) and analyze for variations with age and anatomical region. The posterior scleral cup of 8 eyes from 6 human donors was mounted onto a custom inflation chamber. A laser-scanning microscope was used for second harmonic generation (SHG) imaging of the collagen structure in the posterior volume of the LC at pressures from 5mmHg to 45mmHg. The SHG volumes were analyzed by the Fast-Fourier Iterative Digital Volume Correlation (DVC) algorithm for the three dimensional (3D) displacement field. The components of the Green-Lagrange strain tensor and the in-plane principal and maximum shear strains were evaluated from the DVC displacement field for the central and peripheral regions of the LC and the nasal, temporal, inferior, and superior quadrants surrounding the central retinal artery and vein. Among the major findings were that older age was associated with lower strains, the maximum shear strain was larger in the peripheral than central region, and the maximum principal strain was lower in the nasal quadrant. The elliptical shape of the LC was also predictive of the biaxial strain ratio. Age-related and structure-related variations in the pressure-induced strains of the LC may contribute to the susceptibility and severity of optic nerve damage in glaucoma, and regional variations may explain the progression of axonal damage and tissue remodeling observed in the LC in glaucoma.Statement of significanceGlaucoma causes vision loss through progressive damage of the retinal ganglion axons at the lamina cribrosa (LC), the connective tissue structure that supports the axons as they leave the eye. Mechanical characterization of the LC is challenging because of the complex 3D shape and inaccessibility of the tissue. We present a new method using digital volume correlation to map the 3D displacement and strain fields in the LC under inflation. We report for the first time significant regional variations in the strains that are consistent with the pattern of optic nerve damage in early glaucoma. Thus regional strain variations may be predictive of the progression of axonal damage in glaucoma.

Project description:This study investigated the inflation response of the lamina cribrosa (LC) and adjacent peripapillary sclera (PPS) in post-mortem human eyes with no history of glaucoma. The posterior sclera of 13 human eyes from 7 donors was subjected to controlled pressurization between 5-45 mmHg. A laser-scanning microscope (LSM) was used to image the second harmonic generation (SHG) response of collagen and the two-photon fluorescent (TPF) response of elastin within the volume of the LC and PPS at each pressure. Image volumes were analyzed using digital volume correlation (DVC) to calculate the three-dimensional (3D) deformation field between pressures. The LC exhibited larger radial strain, Err, and maximum principal strain, Emax, (p < 0.0001) and greater posterior displacement (p=0.0007) compared to the PPS between 5-45 mmHg, but had similar average circumferential strain, Eθθ, and maximum shear strain, Γmax. The Emax and Γmax were highest near the LC-PPS interface and lowest in the nasal quadrant of both tissues. Larger LC area was associated with smaller Emax in the peripheral LC and larger Emax in the central LC (p ≤ 0.01). The Emax, Γmax, and Eθθ in the inner PPS increased with increasing strain in adjacent LC regions (p ≤ 0.001). Smaller strains in the PPS were associated with a larger difference in the posterior displacement between the PPS and central LC (p < 0.0001 for Emax and Err), indicating that a stiffer pressure-strain response of the PPS is associated with greater posterior bowing of the LC. STATEMENT OF SIGNIFICANCE: Glaucoma causes vision loss through progressive damage of the retinal ganglion axons at the lamina cribrosa (LC), a connective tissue structure that supports the axons as they pass through the eye wall. It is hypothesized that strains caused by intraocular pressure may initiate this damage and that these strains are modulated by the combined deformation of the LC and adjacent peripapillary sclera (PPS). In this study we present a method to measure the pressure-induced 3D displacement and strain field in the LC and PPS simultaneously. Regional strain variation in the LC and PPS was investigated and compared and strains were analyzed for associations with age, LC area, LC strain magnitude, and LC posterior motion relative to the PPS.

Dataset Information

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

Publications

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

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