Stretch-Induced Uncrimping of Equatorial Sclera Collagen Bundles

Jan, Ning-Jiun; Lee, Po-Yi; Wallace, Jacob; Iasella, Michael; Gogola, Alexandra; Sigal, Ian A.

doi:10.1101/2022.09.13.507860

Cited by 3 publications

(5 citation statements)

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“…(Chung et al, 2016) More detailed experimental information on the anisotropy of the sclera, both in terms of its mechanical behavior and collagen components, will be necessary for more comprehensive models. (Hua et al, 2022;Jan et al, 2022) Lastly, experimental measurement of whole-globe collagen fiber recruitment with IOP is not possible yet with current imaging techniques, making it difficult to validate our model predictions.…”

Section: Discussionmentioning

confidence: 95%

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Who bears the load? IOP-induced collagen fiber recruitment over the corneoscleral shell

Foong

Hua

Amini

et al. 2022

Preprint

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Collagen is the main load-bearing component of cornea and sclera. When stretched, both of these tissues exhibit a behavior known as collagen fiber recruitment. In recruitment, as the tissues stretch the constitutive collagen fibers lose their natural waviness, progressively straightening. Recruited, straight, fibers bear substantially more mechanical load than non-recruited, wavy, fibers. As such, the process of recruitment underlies the well-established nonlinear macroscopic behavior of the corneoscleral shell. Recruitment has an interesting implication: when recruitment is incomplete, only a fraction of the collagen fibers is actually contributing to bear the loads, with the rest remaining in reserve. In other words, at a given intraocular pressure (IOP), it is possible that not all the collagen fibers of the cornea and sclera are actually contributing to bear the loads. To the best of our knowledge, the fraction of corneoscleral shell fibers recruited and contributing to bear the load of IOP has not been reported. Our goal was to obtain regionally-resolved estimates of the fraction of corneoscleral collagen fibers recruited and in reserve. We developed a fiber-based microstructural constitutive model that could account for collagen fiber undulations or crimp via their tortuosity. We used experimentally-measured collagen fiber crimp tortuosity distributions in human eyes to derive region-specific nonlinear hyperelastic mechanical properties. We then built a three-dimensional axisymmetric model of the globe, assigning region-specific mechanical properties and regional anisotropy. The model was used to simulate the IOP-induced shell deformation. The model-predicted tissue stretch was then used to quantify collagen recruitment within each shell region. The calculations showed that, at low IOPs, collagen fibers in the posterior equator were recruited the fastest, such that at a physiologic IOP of 15 mmHg, over 90% of fibers were recruited, compared with only a third in the cornea and the peripapillary sclera. The differences in recruitment between regions, in turn, mean that at a physiologic IOP the posterior equator had a fiber reserve of only 10%, whereas the cornea and peripapillary sclera had two thirds. At an elevated IOP of 50 mmHg, collagen fibers in the limbus and the anterior/posterior equator were almost fully recruited, compared with 90% in the cornea and the posterior sclera, and 75% in the peripapillary sclera and the equator. That even at such an elevated IOP not all the fibers were recruited suggests that there are likely other conditions that challenge the corneoscleral tissues even more than IOP. The fraction of fibers recruited may have other potential implications. For example, fibers that are not bearing loads may be more susceptible to enzymatic digestion or remodeling. Similarly, it may be possible to control tissue stiffness through the fraction of recruited fibers without the need to add or remove collagen.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Who bears the load? IOP-induced collagen fiber recruitment over the corneoscleral shell

Foong

Hua

Amini

et al. 2022

Preprint

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“…From a mechanical perspective, the undulations of crimp affect directly the biomechanical behavior of a fiber under load, with the crimp "disappearing" as the fiber is loaded or stretched, and eventually recruited (Jan et al, 2022;. The interactions between interwoven fibers mean that these undulations do not "disappear" under load, and are limited by the interlocking (Lee et al, 2022b).…”

Section: Discussionmentioning

confidence: 99%

“…For example, ocular collagen fibers crimp has a period typically under 20 μm, (Gogola et al, 2018a; Jan et al, 2018; Jan et al, 2017a; Jan and Sigal, 2018) much smaller than the estimates of interweaving undulations on the order of 100 to 300 μm (Wang et al, 2020). From a mechanical perspective, the undulations of crimp affect directly the biomechanical behavior of a fiber under load, with the crimp “disappearing” as the fiber is loaded or stretched, and eventually recruited (Jan et al, 2022; Jan and Sigal, 2018). The interactions between interwoven fibers mean that these undulations do not “disappear” under load, and are limited by the interlocking (Lee et al, 2022b).…”

Section: Discussionmentioning

confidence: 99%

A direct fiber approach to model sclera collagen architecture and biomechanics

Bansal

Wang

et al. 2022

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Sclera collagen fiber microstructure and mechanical behavior are central to eye physiology and pathology. They are also complex, and are therefore often studied using modeling. Most models of sclera, however, have been built within a conventional continuum framework. In this framework, collagen fibers are incorporated as statistical distributions of fiber characteristics such as the orientation of a family of fibers. The conventional continuum approach, while proven successful for describing the macroscale behavior of the sclera, does not account for the sclera fibers are long, interwoven and interact with one another. Hence, by not considering these potentially crucial characteristics, the conventional approach has only a limited ability to capture and describe sclera structure and mechanics at smaller, fiber-level, scales. Recent advances in the tools for characterizing sclera microarchitecture and mechanics bring to the forefront the need to develop more advanced modeling techniques that can incorporate and take advantage of the newly available highly detailed information. Our goal was to create a new modeling approach that can represent the sclera fibrous microstructure more accurately than with the conventional continuum approach, while still capturing its macroscale behavior. In this manuscript we introduce the new modeling approach, that we call direct fiber modeling, in which the collagen architecture is built explicitly by long, continuous, interwoven fibers. The fibers are embedded in a continuum matrix representing the non-fibrous tissue components. We demonstrate the methodology by modeling a rectangular patch of the posterior sclera. The direct fiber model presented incorporated specimen-specific fiber orientations derived from polarized light microscopy data of histological cryosections. The fibers were modeled using a Mooney-Rivlin model, and the matrix using a Neo-Hookean model. The fiber parameters were determined by inversely matching experimental equi-biaxial tensile data from the literature. After reconstruction, the direct fiber model orientations agreed well with the microscopy data both in the coronal plane (adjusted R2=0.8234) and in the sagittal plane (adjusted R2=0.8495) of the sclera. With the estimated fiber properties (C10=5746.9 MPa; C01=-5002.6MPa, matrix shear modulus 200kPa), the model`s stress-strain curves simultaneously fit the experimental data in radial and circumferential directions (adjusted R2`s 0.9971 and 0.9508, respectively). The estimated fiber elastic modulus at 2.16% strain was 5.45GPa, in reasonable agreement with the literature. During stretch, the model exhibited stresses and strains at sub-fiber level, with interactions among individual fibers which are not accounted for by the conventional continuum methods. Our results demonstrate that direct fiber models can simultaneously describe the macroscale mechanics and microarchitecture of the sclera, and therefore that the approach can provide unique insight into tissue behavior questions inaccessible with continuum approaches.

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“…For static imaging, Sample preparation for uniaxial stretch testing. An unfixed sheep eye section was prepared as described in detail previously (Jan et al, 2022). Briefly, a normal one-year-old sheep eye was obtained from a local abattoir within four hours after death.…”

Section: Imaging Collagen Architecture and Deformationmentioning

confidence: 99%

Instant polarized light microscopy pi (IPOLπ) for quantitative imaging of collagen architecture and dynamics in ocular tissues

Lee

Schilpp

Naylor

et al. 2023

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Collagen architecture determines the biomechanical environment in the eye, and thus characterizing collagen fiber organization and biomechanics is essential to fully understand eye physiology and pathology. We recently introduced instant polarized light microscopy (IPOL) that encodes optically information about fiber orientation and retardance through a color snapshot. Although IPOL allows imaging collagen at the full acquisition speed of the camera, with excellent spatial and angular resolutions, a limitation is that the orientation-encoding color is cyclic every 90 degrees (π/2 radians). In consequence, two orthogonal fibers have the same color and therefore the same orientation when quantified by color-angle mapping. In this study, we demonstrate IPOLπ, a new variation of IPOL, in which the orientation-encoding color is cyclic every 180 degrees (π radians). Herein we present the fundamentals of IPOLπ, including a framework based on a Mueller-matrix formalism to characterize how fiber orientation and retardance determine the color. The improved quantitative capability of IPOLπ enables further study of essential biomechanical properties of collagen in ocular tissues, such as fiber anisotropy and crimp. We present a series of experimental calibrations and quantitative procedures to visualize and quantify ocular collagen orientation and microstructure in the optic nerve head, a region in the back of the eye. There are four important strengths of IPOLπ compared to IPOL. First, IPOLπ can distinguish the orientations of orthogonal collagen fibers via colors, whereas IPOL cannot. Second, IPOLπ requires a lower exposure time than IPOL, thus allowing faster imaging speed. Third, IPOLπ allows visualizing non-birefringent tissues and backgrounds from tissue absorption, whereas both appear dark in IPOL images. Fourth, IPOLπ is cheaper and less sensitive to imperfectly collimated light than IPOL. Altogether, the high spatial, angular, and temporal resolutions of IPOLπ enable a deeper insight into ocular biomechanics and eye physiology and pathology.

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Stretch-Induced Uncrimping of Equatorial Sclera Collagen Bundles

Cited by 3 publications

References 60 publications

Who bears the load? IOP-induced collagen fiber recruitment over the corneoscleral shell

Who bears the load? IOP-induced collagen fiber recruitment over the corneoscleral shell

A direct fiber approach to model sclera collagen architecture and biomechanics

Instant polarized light microscopy pi (IPOLπ) for quantitative imaging of collagen architecture and dynamics in ocular tissues

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