The hierarchical response of human corneal collagen to load (original) (raw)
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Proceedings of the National Academy of Sciences, 2001
The ability of the cornea to transmit light while being mechanically resilient is directly attributable to the formation of an extracellular matrix containing orthogonal sheets of collagen fibrils. The detailed structure of the fibrils and how this structure underpins the mechanical properties and organization of the cornea is understood poorly. In this study, we used automated electron tomography to study the three-dimensional organization of molecules in corneal collagen fibrils. The reconstructions show that the collagen molecules in the 36-nm diameter collagen fibrils are organized into microfibrils (≈4-nm diameter) that are tilted by ≈15° to the fibril long axis in a right-handed helix. An unexpected finding was that the microfibrils exhibit a constant-tilt angle independent of radial position within the fibril. This feature suggests that microfibrils in concentric layers are not always parallel to each other and cannot retain the same neighbors between layers. Analysis of the ...
Investigative Ophthalmology & Visual Science, 2009
PURPOSE. To study the distribution and predominant orientations of fibrillar collagen at different depths throughout the entire thickness of the human cornea. This information will form the basis of a full three-dimensional reconstruction of the preferred orientations of corneal lamellae. METHODS. Femtosecond laser technology was used to delaminate the central zones of five human corneas into three separate layers (anterior, mid, and posterior stroma), each with predetermined thicknesses. Wide-angle x-ray diffraction was used to study the gross collagen fibril orientation and distribution within each layer. RESULTS. The middle and posterior parts of the human cornea demonstrated a preferential orthogonal arrangement of collagen fibrils, directed along the superior-inferior and nasaltemporal meridians, with an increase in the number of lamellae toward the periphery. However, the anterior cornea (33% of total corneal thickness) showed no systematic preferred lamellar orientation. CONCLUSIONS. In the posterior two thirds of the human cornea, collagen lies predominantly in the vertical and horizontal meridians (directed toward the four major rectus muscles), whereas collagen in the anterior third of the cornea is more isotropic. The predominantly orthogonal arrangement of collagen in the mid and posterior stroma may help to distribute strain in the cornea by allowing it to withstand the pull of the extraocular muscles, whereas the more isotropic arrangement in the anterior cornea may play an important role in the biomechanics of the cornea by resisting intraocular pressure while at the same time maintaining corneal curvature. (Invest
Nonlinear Optical Macroscopic Assessment of 3-D Corneal Collagen Organization and Axial Biomechanics
Investigative Opthalmology & Visual Science, 2011
PURPOSE. To characterize and quantify the collagen fiber (lamellar) organization of human corneas in three dimensions by using nonlinear optical high-resolution macroscopy (NLO-HRMac) and to correlate these findings with mechanical data obtained by indentation testing of corneal flaps. METHODS. Twelve corneas from 10 donors were studied. Vibratome sections, 200 m thick, from five donor eyes were cut along the vertical meridian from limbus to limbus (arc length, 12 mm). Backscattered second harmonic-generated (SHG) NLO signals from these sections were collected as a series of overlapping 3-D images, which were concatenated to form a single 3-D mosaic (pixel resolution: 0.44 m lateral, 2 m axial). Collagen fiber intertwining was quantified by determining branching point density as a function of stromal depth. Mechanical testing was performed on corneal flaps from seven additional eyes. Corneas were cut into three layers (anterior, middle, and posterior) using a femtosecond surgical laser system and underwent indentation testing to determine the elastic modulus for each layer. RESULTS. The 3-D reconstructions revealed complex collagen fiber branching patterns in the anterior cornea, with fibers extending from the anterior limiting lamina (ALL, Bowman's layer), intertwining with deeper fibers and reinserting back to the ALL, forming bow spring-like structures. Measured branching-point density was four times higher in the anterior third of the cornea than in the posterior third and decreased logarithmically with increasing distance from the ALL. Indentation testing showed an eightfold increase in elastic modulus in the anterior stroma. CONCLUSIONS. The axial gradient in lamellar intertwining appears to be associated with an axial gradient in the effective elastic modulus of the cornea, suggesting that collagen fiber intertwining and formation of bow spring-like structures provide structural support similar to cross-beams in bridges and large-scale structures. Future studies are necessary to determine the role of radial and axial structural-mechanical heterogeneity in controlling corneal shape and in the development of keratoconus, astigmatism, and other refractive errors. (In
ZAMM - Journal of Applied Mathematics and Mechanics / Zeitschrift für Angewandte Mathematik und Mechanik, 2018
We present a finite element model of the human cornea describing the in-plane organization of the stromal collagen, modified variously to include features of the collagen architecture. We investigate numerically the implication of the local organization of collagen in the stroma on the response of the human cornea to mechanical tests. We compare four different models by simulating three ideal mechanical tests, i. e., the ex-vivo inflation test, the in-vivo probe indentation, and the in-vivo air puff tests. Numerical results show slight differences between the models in terms of global response and stress distribution. Differences in the overall mechanical response are observed in dynamic tests, while quasi-static tests are not able to differentiate between the models. Stress distributions differ markedly when a variation of the shear stiffness across the thickness is considered. We conclude that the actual architecture of the collagen across the thickness of the cornea or at the limbus has a minor relevance from the mechanical point of view with respect to the main anisotropic orthogonal collagen structure that has been considered and acknowledged in the literature.
Quantification of Collagen Organization in the Peripheral Human Cornea at Micron-Scale Resolution
Biophysical Journal, 2011
The collagen microstructure of the peripheral cornea is important in stabilizing corneal curvature and refractive status. However, the manner in which the predominantly orthogonal collagen fibrils of the central cornea integrate with the circumferential limbal collagen is unknown. We used microfocus wide-angle x-ray scattering to quantify the relative proportion and orientation of collagen fibrils over the human corneolimbal interface at intervals of 50 mm. Orthogonal fibrils changed direction 1-1.5 mm before the limbus to integrate with the circumferential limbal fibrils. Outside the central 6 mm, additional preferentially aligned collagen was found to reinforce the cornea and limbus. The manner of integration and degree of reinforcement varied significantly depending on the direction along which the limbus was approached. We also employed small-angle x-ray scattering to measure the average collagen fibril diameter from central cornea to limbus at 0.5 mm intervals. Fibril diameter was constant across the central 6 mm. More peripherally, fibril diameter increased, indicative of a merging of corneal and scleral collagen. The point of increase varied with direction, consistent with a scheme in which the oblique corneal periphery is reinforced by chords of scleral collagen. The results have implications for the cornea's biomechanical response to ocular surgeries involving peripheral incision.
Experimental study on the mechanical strain of corneal collagen
Currently, investigations of biomechanical properties of the fibrous tunic are becoming even more topical, especially for diagnosis of corneal ectatic disease, as well as correct interpretation of intraocular pressure (IOP) parameters, particularly in patients with prior surgery on cornea. The study principle is based on the ability of substances to change optical anisotropy depending on mechanical strain applied to them. An experimental set-up was constructed which allows assessment of polarization degree of light which is emitted during luminescence of strained collagen. The study was performed on 18 corneoscleral discs of chinchilla rabbit eyes at 15 and 50 mm Hg pressure, among them in 6 cases before and after making radial incisions, and in 6 cases before and after conducting the mechanical cornea abrasions that were asymmetrical by depth until reaching the local zone of iatrogenic keratectasia. Corneal collagen mechanical strain mappings were formed on 3 experimental models (intact cornea, cornea post radial keratotomy and keratectasia) under intra-chamber pressure of 15 and 50 mm Hg. Corneal collagen mechanical strain is evenly allocated in the intact cornea. After radial keratotomy the main mechanical loading was concentrated over the middle part of corneal periphery, particularly in the bottom of keratotomic incisions. The increased intra-chamber pressure made the strain rise in those models. Upon cornea abrasion the main straining is distributed within the thinning zone, and the increase of intra-chamber pressure only increases the load over residual stroma. A new principle of corneal biomechanical properties investigation based on assessment of degree of light polarization emitted during luminescence of strained collagen, has been proposed and experimentally tested.
Corneal Biomechanical Changes after Collagen Cross-Linking from Porcine Eye Inflation Experiments
Investigative Ophthalmology & Visual Science, 2010
Understanding corneal biomechanics is important to refractive or therapeutic corneal treatments. The authors studied the corneal response to variable intraocular pressure (IOP) in porcines eyes after UV collagen cross-linking (CXL), in comparison with untreated eyes. METHODS. Twenty-three enucleated eyes were treated with standard CXL conditions (365 nm, 3 mW, 30 minutes), and 15 contralateral eyes served as control. Eyes (within a humidityand temperature-monitored wet chamber) were measured by Scheimpflug corneal three-dimensional topographer. Images were obtained automatically while IOP either remained constant (14 eyes) or increased (24 eyes) by 40 mm Hg and then decreased (4-mm Hg steps). Measurements were performed immediately after treatment and 24 hours later. Corneal geometry was analyzed as a function of IOP, and whole globe stress-strain curves were calculated. RESULTS. Instillation of riboflavin-dextran solution reduced corneal thickness (by 281 Ϯ 5 m). Cross-linking produced a 1.54ϫ reduction in corneal thinning and 2.8ϫ reduction in corneal apical rise with increased IOP. Anterior and posterior cornea flattened with increased IOP (less flattening in CXL eyes) and became steeper with decreased IOP. The horizontal meridian flattened significantly (P Ͻ 0.01) more than the vertical meridian. Young's modulus was higher in cross-linked eyes (1.096 Ϯ 0.30 kN/m 2 ) than in non-cross-linked eyes (0.692 Ϯ 0.30 kN/m 2 ). Hysteresis in nontreated eyes was also larger than in cross-linked eyes. CONCLUSIONS. Cross-linking stiffened porcine corneas significantly. Both experimental data and stress-strain analysis are valuable for finite element models to improve understanding of CXL and its predictability. Although differences are expected between human corneas in vivo and porcine corneas ex vivo, the results are consistent with clinical data found in patients.
Mapping Collagen Organization in the Human Cornea: Left and Right Eyes Are Structurally Distinct
Investigative Opthalmology & Visual Science, 2006
PURPOSE. Aspects of the biomechanics and surface topography of fellow human corneas are known to exhibit midline symmetry, but the structural basis of these observations is poorly understood. The mechanical performance of the cornea is strongly influenced by the organization of stromal collagen fibrils. The present study was designed to examine and compare the organization of collagen fibrils in the corneal stroma of left and right eyes. METHODS. Wide-angle x-ray scattering was used to map in detail the orientation and distribution of fibrillar collagen across the cornea, limbus, and adjacent sclera of three normal human eyes, including a fellow pair, and the central 9-mm corneal region of a further four eyes. RESULTS. Fibrillar collagen in the human cornea and limbus is arranged anisotropically, and in a highly specific manner. Left and right corneas are structurally distinct. In general, the mass distribution of preferentially aligned fibrils in the cornea appears to exhibit a degree of midline symmetry between left and right eyes. CONCLUSIONS. Structural information, such as that presented herein, will enable a better understanding of corneal biomechanics and shape. Midline symmetry in the distribution of aligned, mechanically reinforcing collagen fibrils between left and right eyes may relate to the biomechanical and topographical enantiomorphism reported in the literature.
Numerical Simulation of Corneal Fibril Reorientation in Response to External Loading
International Journal of Environmental Research and Public Health
Purpose: To simulate numerically the collagen fibril reorientation observed experimentally in the cornea. Methods: Fibril distribution in corneal strip specimens was monitored using X-ray scattering while under gradually increasing axial loading. The data were analysed at each strain level in order to quantify the changes in the angular distribution of fibrils with strain growth. The resulting relationship between stain and fibril reorientation was adopted in a constitutive model to control the mechanical anisotropy of the tissue material. The outcome of the model was validated against the experimental measurements before using the model in simplified representations of two surgical procedures. Results: The numerical model was able to reproduce the experimental measurements of specimen deformation and fibril reorientation under uniaxial loading with errors below 8.0%. With tissue removal simulated in a full eye numerical model, fibril reorientation could be predicted around the affe...
PLOS ONE, 2019
This study aimed to analyse microstructure data on the density and orientation of collagen fibrils in whole eye globes and to propose an effective method for the preparation of data for use in numerical simulations of the eye's biomechanical performance. Wide-angle X-ray scattering was applied to seven healthy ex-vivo human eyes. Each eye was dissected into an anterior and a posterior cup, and radial incisions were used to flatten the tissue before microstructure characterisation. A method was developed to use the microstructure data obtained for the dissected tissue to build realistic 3D maps of fibril density and orientation covering the whole eye globe. At the central cornea, 61.5±2.3% of fibrils were aligned within 45˚sectors surrounding the two orthogonal directions. In contrast, more than one-third of the total fibril content was concentrated along the circumferential direction at the limbus (37.0±2.4%) and around the optic nerve head (34.8±2.1%). The insertion locations of the four recti muscles exhibited a preference in the meridional direction near the equator (38.6 ±3.9%). There was also a significant difference in fibril density between the limbus and other regions (ratio = 1.91±0.45, p <0.01 at the central cornea and ratio = 0.80±0.21, p <0.01 at the posterior pole). Characterisation of collagen fibril density and orientation across the whole ocular surface has been possible but required the use of a technique that involved tissue dissection and hence caused tissue damage. The method presented in this paper aimed to minimise the effect of dissection on the quality of obtained data and was successful in identifying fibril distribution trends that were compatible with earlier studies, which concentrated on localised areas of the ocular globe.