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The inflation response of the human lamina cribrosa and sclera: Analysis of deformation and interaction.

ABSTRACT: 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, E_rr, and maximum principal strain, E_max, (p < 0.0001) and greater posterior displacement (p=0.0007) compared to the PPS between 5-45 mmHg, but had similar average circumferential strain, E_θθ, and maximum shear strain, Γ_max. The E_max and Γ_max were highest near the LC-PPS interface and lowest in the nasal quadrant of both tissues. Larger LC area was associated with smaller E_max in the peripheral LC and larger E_max in the central LC (p ≤ 0.01). The E_max, Γ_max, and E_θθ 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 E_max and E_rr), 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.

SUBMITTER: Midgett DE

PROVIDER: S-EPMC8340454 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.Glaucoma 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:Glaucoma is the second leading cause of irreversible blindness in the world with a higher prevalence in those of African Descent (AD) and Hispanic Ethnicity (HE) than in those of European Descent (ED). The objective of this study was to investigate the pressure dependent biomechanical response of the lamina cribrosa (LC) in normal human donor tissues from these racioethnic backgrounds. Pressure inflation tests were performed on 24 human LCs (n = 9 AD, n = 6 ED, and n = 9 HE) capturing the second harmonic generation (SHG) signal of collagen at 5, 15, 30, and 45 mmHg from an anterior view. A non-rigid image registration technique was utilized to determine the 3D displacement field in each LC from which 3D Green strains were calculated. The peak shear strain in the superior quadrant of the LC in those of ED was significantly higher than in those of AD and HE (p-value = 0.005 & 0.034, respectively) where ED = 0.017 [IQR = 0.012-0.027], AD = 0.0002 [IQR = -0.001-0.007], HE = 0.0016 [IQR = -0.002-0.012]). There were also significant differences in the regional strain heterogeneity in those of AD and HE that were absent in those of ED. This work represents, to our knowledge, the first ex-vivo study identifying significant differences in the biomechanical response of the LC in populations at increased risk of glaucoma. Future work will be necessary to assess if and how these differences play a role in predisposing those of Hispanic Ethnicity and African Descent to the onset and/or progression of primary open angle glaucoma. STATEMENT OF SIGNIFICANCE: Glaucoma is the second leading cause of irreversible blindness in the world and occurs more frequently in those of African Descent and Hispanic Ethnicity than in those of European Descent. To date, there has been no ex-vivo study quantifying differences in the biomechanical response of the non-glaucomatous lamina cribrosa (LC) across these racioethnic backgrounds. In this work we report, for the first time, differences in the pressure dependent biomechanical response of LC across different racioethnic groups as quantified using nonlinear optical microscopy. This study lays the foundation for future work investigating if and how these differences may play a role in predisposing those at increased risk to the onset and/or progression of primary open angle glaucoma.

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.

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The inflation response of the human lamina cribrosa and sclera: Analysis of deformation and interaction.

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