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Thin Lamina Cribrosa Beams Have Different Collagen Microstructure Than Thick Beams.

ABSTRACT: Purpose:To compare the collagen microstructural crimp characteristics between thin and thick lamina cribrosa (LC) beams. Methods:Seven eyes from four sheep were fixed at 5 mm Hg IOP in 10% formalin. For each eye, one to three coronal cryosections through the LC were imaged with polarized light microscopy and analyzed to visualize the LC and determine collagen fiber microstructure. For every beam, we measured its width and three characteristics of the crimp of its collagen fibers: waviness, tortuosity, and amplitude. Linear mixed effects models were used to test whether crimp characteristics were associated with the LC beam width. Results:For each eye and over all the eyes, LC beam width was positively associated with crimp waviness and tortuosity, and negatively associated with crimp amplitude (P's < 0.0001). Thin beams, average width 13.11 ?m, had average (SD) waviness, tortuosity, and amplitude of 0.27 (0.17) radians, 1.017 (0.028) and 1.88 (1.41) ?m, respectively. For thick beams, average width 26.10 ?m, these characteristics were 0.33 (0.18) radians, 1.025 (0.037) and 1.58 (1.36) ?m, respectively. Conclusions:Our results suggest heterogeneity in LC beam mechanical properties. Thin beams were less wavy than their thicker counterparts, suggesting that thin beams may stiffen at lower IOP than thick beams. This difference may allow thin beams to support similar amounts of IOP-induced force as thicker beams, thus providing a similar level of structural support to the axons at physiologic IOP, despite the differences in width. Measurements of beam-level mechanical properties are needed to confirm these predictions.

SUBMITTER: Brazile BL

PROVIDER: S-EPMC6149225 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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Thin Lamina Cribrosa Beams Have Different Collagen Microstructure Than Thick Beams.

Brazile Bryn L BL Hua Yi Y Jan Ning-Jiun NJ Wallace Jacob J Gogola Alexandra A Sigal Ian A IA

Investigative ophthalmology & visual science 20180901 11

<h4>Purpose</h4>To compare the collagen microstructural crimp characteristics between thin and thick lamina cribrosa (LC) beams.<h4>Methods</h4>Seven eyes from four sheep were fixed at 5 mm Hg IOP in 10% formalin. For each eye, one to three coronal cryosections through the LC were imaged with polarized light microscopy and analyzed to visualize the LC and determine collagen fiber microstructure. For every beam, we measured its width and three characteristics of the crimp of its collagen fibers: ...[more]

PMID: 30372734

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Project description: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.

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.

Dataset Information

Thin Lamina Cribrosa Beams Have Different Collagen Microstructure Than Thick Beams.

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Thin Lamina Cribrosa Beams Have Different Collagen Microstructure Than Thick Beams.

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