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Experimental Eye Research Feb 2023The purpose of this study was to investigate the efficacy and safety of microbial transglutaminases (mTGases) during scleral collagen cross-linking (CXL) in vivo....
The purpose of this study was to investigate the efficacy and safety of microbial transglutaminases (mTGases) during scleral collagen cross-linking (CXL) in vivo. Sixteen New Zealand white albino rabbits were treated with sub-Tenon's injections of 2 ml of 1 U/ml mTGases in the right eye and 2 ml of phosphate buffer saline (PBS) in the left eye. The rabbits were killed 2 weeks after the injection, and all eyeballs, including some scleral strips, were processed. The elastic modulus was measured with a biomaterials tester. Histopathological analysis and transmission electron microscopy (TEM) were used for the morphological observations. The elastic modulus of the mTGase-treated sclera was 15.79 ± 2.93 MPa, and that of the control was 6.91 ± 2.23 MPa, indicating an increase of 129% after the mTGases treatment (P < 0.05). The density of the scleral collagen bundles and diameter of the collagen fibrils increased compared with those in the control group. No apoptosis was detected in the retina or posterior sclera by TUNEL staining, and no histological damage was observed on the TEM scan. This study is based on a short-term study on animal models. These results indicate that mTGase-mediated scleral CXL is a promising approach to effectively stiffen the sclera and safe enough for retina, and may be a useful treatment modality for strengthening scleral tissue.
Topics: Animals; Rabbits; Sclera; Elastic Modulus; Retina; Disease Models, Animal; Collagen; Cross-Linking Reagents
PubMed: 36646298
DOI: 10.1016/j.exer.2023.109387 -
Experimental Eye Research Jul 2023Sclera collagen fiber microstructure and mechanical behavior are central to eye physiology and pathology. They are also complex, and are therefore often studied using...
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 computational 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 approach by doing direct fiber modeling of a rectangular patch of posterior sclera. The model integrated fiber orientations obtained by polarized light microscopy from coronal and sagittal cryosections of pig and sheep. 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 R = 0.8234) and in the sagittal plane (adjusted R = 0.8495) of the sclera. With the estimated fiber properties (C = 5746.9 MPa; C = -5002.6 MPa, matrix shear modulus 200 kPa), the model's stress-strain curves simultaneously fit the experimental data in radial and circumferential directions (adjusted R's 0.9971 and 0.9508, respectively). The estimated fiber elastic modulus at 2.16% strain was 5.45 GPa, 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.
Topics: Swine; Animals; Sheep; Sclera; Biomechanical Phenomena; Models, Biological; Collagen; Extracellular Matrix; Stress, Mechanical
PubMed: 37207867
DOI: 10.1016/j.exer.2023.109510 -
Current Eye Research Jun 2020: Corneal collagen cross-linking by ultraviolet light activation of riboflavin has been used clinically to enhance corneal stiffness. We sought to determine if...
: Corneal collagen cross-linking by ultraviolet light activation of riboflavin has been used clinically to enhance corneal stiffness. We sought to determine if cross-linking differentially affects scleral regions.: Adjacent, parallel strips of sclera were cut from superolateral, superomedial, inferolateral, and inferomedial quadrants of posterior and equatorial sclera of 12 human cadaver eyes. One of each pair served as control while the other was cross-linked by immersion in 0.1% riboflavin and 365 nm exposure at 6 mW/cm irradiance for 30 min. Behavior of strips was characterized using a microtensile load cell. Preloaded strips were imaged using orthogonally mounted cameras and optical coherence tomography to determine specimen dimensions including cross-sectional area. Tension was measured during 0.1 mm/s constant rate elongation.: Young's modulus (YM), the slope of the relationship relating tensile stress to strain, was calculated at 8% strain, and increased significantly after cross-linking ( < .001). In posterior sclera, mean (± standard error of mean, SEM) YM is increased in the superolateral, superomedial, inferolateral, and inferomedial quadrants by 46 ± 15%, 32 ± 11%, 67 ± 20%, and 53 ± 11%, respectively. In equatorial sclera, YM is increased by 139 ± 43%, 68 ± 27%, 143 ± 92%, and 68 ± 14%, respectively. The YM of pooled equatorial quadrants increased significantly more than that of the pooled posterior quadrants.: Scleral collagen cross-linking by ultraviolet activation of riboflavin differentially increases scleral YM more in the equatorial than posterior sclera, and most in the lateral, equatorial sclera. Cross-linking might be used to arrest progressive myopia or to prevent staphyloma formation.
Topics: Biomechanical Phenomena; Collagen; Cross-Linking Reagents; Elastic Modulus; Humans; Photochemotherapy; Photosensitizing Agents; Riboflavin; Sclera; Tensile Strength; Tomography, Optical Coherence; Ultraviolet Rays
PubMed: 31735063
DOI: 10.1080/02713683.2019.1694157 -
Acta Biomaterialia Apr 2022The sclera provides mechanical support to retina and protects internal contents of the eye against external injuries. The scleral extracellular matrix is mainly composed...
The sclera provides mechanical support to retina and protects internal contents of the eye against external injuries. The scleral extracellular matrix is mainly composed of collagen fibers and proteoglycans (PGs). At physiological pH, collagen molecules are neutral but PGs contain negatively charged glycosaminoglycan chains. Thus, the sclera can be considered as a polyelectrolyte hydrogel and is expected to exhibit mechanical response when subjected to electrical stimulations. In this study, we mounted scleral strips, dissected from the posterior part of porcine eyes, at the center of a custom-designed container between two electrodes. The container was filled with NaCl solution and the bending deformation of scleral strips as a function of the applied electric voltage was measured experimentally. It was found that scleral strips reached to an average bending angle of 3°, 10° and 23° when subjected to 5V, 10V, and 15V, respectively. We also created a chemo-electro-mechanical finite element model for simulating the experimental measurements by solving coupled Poisson-Nernst-Plank and equilibrium mechanical field equations. The scleral fixed charge density and modulus of elasticity were found by fitting the experimental data. The ion concentration distribution inside the domain was found numerically and was used to explain the underlying mechanisms for the scleral electroactive response. The numerical simulations were also used to investigate the effects of various parameters such as the electric voltage and fixed charge density on the scleral deformation under an electric field. STATEMENT OF SIGNIFICANCE: This manuscript investigates the electroactive response of scleral tissue. It demonstrates that the sclera deforms mechanically when subjected to electrical stimulations. A chemo-electro-mechanical model is also presented in order to numerically capture the electromechanical response of the sclera. This numerical model is used to explain the experimental observations by finding the ion distribution inside the tissue under an electric field. This work is significant because it shows that the sclera is an electroactive polyanionic hydrogel and it provides new information about the underlying mechanisms governing its mechanical and electrical properties.
Topics: Animals; Biomechanical Phenomena; Collagen; Elasticity; Hydrogels; Sclera; Swine
PubMed: 35038585
DOI: 10.1016/j.actbio.2022.01.017 -
Journal of Cataract and Refractive... Nov 2020
Topics: Lenses, Intraocular; Sclera; Sutures
PubMed: 33149078
DOI: 10.1097/j.jcrs.0000000000000429 -
PloS One 2020To assess the axial, radial and tangential limbus position misrepresentation when parametric models are used to represent the cornea and the sclera.
PURPOSE
To assess the axial, radial and tangential limbus position misrepresentation when parametric models are used to represent the cornea and the sclera.
METHODS
This retrospective study included 135 subjects aged 22 to 65 years (36.5 mean ±9.8 STD), 71 females and 64 males. Topography measurements were taken using an Eye Surface Profiler topographer and processed by a custom-built MATLAB code. Eye surfaces were freed from edge-effect artefacts and fitted to spherical, conic and biconic models.
RESULTS
When comparing the radial position of the limbus, average errors of -0.83±0.19mm, -0.76±0.20mm and -0.69±0.20mm were observed within the right eye population for the spherical, conic and biconic models fitted up to 5mm. For the same fitting radius, the average fitting errors were -0.86±0.23mm, -0.78±0.23mm and -0.73±0.23mm for the spherical, conic and biconic models respectively within the left eye population. For the whole cornea fit, the average errors were -0.27±0.12mm and -0.28±0.13mm for the spherical models, -0.02±0.29mm and -0.05±0.27mm for the conic models, and -0.22±0.16mm and 0.24±0.17mm for the biconic models in the right and left eye populations respectively.
CONCLUSIONS
Through the use of spherical, conic and biconic parametric modelling methods, the eye's limbus is being mislocated. Additionally, it is evident that the magnitude of fitting error associated with the sclera may be propagating through the other components of the eye. This suggests that a corneal nonparametric model may be necessary to improve the representation of the limbus.
Topics: Adult; Aged; Algorithms; Cornea; Corneal Topography; Female; Humans; Male; Middle Aged; Models, Anatomic; Retrospective Studies; Sclera; Young Adult
PubMed: 32970690
DOI: 10.1371/journal.pone.0236096 -
Biomechanics and Modeling in... Aug 2021The optic nerve (ON) is a recently recognized tractional load on the eye during larger horizontal eye rotations. In order to understand the mechanical behavior of the...
The optic nerve (ON) is a recently recognized tractional load on the eye during larger horizontal eye rotations. In order to understand the mechanical behavior of the eye during adduction, it is necessary to characterize material properties of the sclera, ON, and in particular its sheath. We performed tensile loading of specimens taken from fresh postmortem human eyes to characterize the range of variation in their biomechanical properties and determine the effect of preconditioning. We fitted reduced polynomial hyperelastic models to represent the nonlinear tensile behavior of the anterior, equatorial, posterior, and peripapillary sclera, as well as the ON and its sheath. For comparison, we analyzed tangent moduli in low and high strain regions to represent stiffness. Scleral stiffness generally decreased from anterior to posterior ocular regions. The ON had the lowest tangent modulus, but was surrounded by a much stiffer sheath. The low-strain hyperelastic behaviors of adjacent anatomical regions of the ON, ON sheath, and posterior sclera were similar as appropriate to avoid discontinuities at their boundaries. Regional stiffnesses within individual eyes were moderately correlated, implying that mechanical properties in one region of an eye do not reliably reflect properties of another region of that eye, and that potentially pathological combinations could occur in an eye if regional properties are discrepant. Preconditioning modestly stiffened ocular tissues, except peripapillary sclera that softened. The nonlinear mechanical behavior of posterior ocular tissues permits their stresses to match closely at low strains, although progressively increasing strain causes particularly great stress in the peripapillary region.
Topics: Adult; Aged; Aged, 80 and over; Biomechanical Phenomena; Elasticity; Eye; Female; Finite Element Analysis; Head; Humans; Male; Middle Aged; Optic Disk; Optic Nerve; Sclera; Stress, Mechanical; Tensile Strength
PubMed: 33877503
DOI: 10.1007/s10237-021-01448-2 -
Indian Journal of Ophthalmology Feb 2024High myopia is often associated with local ectasia and scleral thinning. The progression of myopia depends upon scleral biochemical and biomechanical properties. Scleral...
High myopia is often associated with local ectasia and scleral thinning. The progression of myopia depends upon scleral biochemical and biomechanical properties. Scleral thinning is associated with decreased collagen fiber diameter, defective collagen fibrillogenesis, and collagen cross-linking. Reversing these abnormalities may make the sclera tougher and might serve as a treatment option for myopic progression. Collagen cross-linking is a natural process in the cornea and sclera, which makes the structure stiff. Exogenous collagen cross-linkage is artificially induced with the help of external mediators by using light and dark methods. In this systematic review, we discussed existing literature available on the internet on current evidence-based applications of scleral collagen cross-linking (SXL) by using different interventions. In addition, we compared them in tabular form in terms of their technique, mechanisms, cytotoxicity, and the stage of transition from preclinical to clinical development. Furthermore, we discussed the in-vivo technique to evaluate the post-SXL scleral biomechanical property and outcome in the human eye.
Topics: Humans; Collagen; Cornea; Cross-Linking Reagents; Myopia, Degenerative; Sclera
PubMed: 38153964
DOI: 10.4103/IJO.IJO_1392_23 -
Current Eye Research Feb 2023Ocular biomechanics is an assessment of the response of the structures of the eye to forces that may lead to disease development and progression, or influence the... (Review)
Review
Ocular biomechanics is an assessment of the response of the structures of the eye to forces that may lead to disease development and progression, or influence the response to surgical intervention. The goals of this review are (1) to introduce basic biomechanical principles and terminology, (2) to provide perspective on the progress made in the clinical study and assessment of ocular biomechanics, and (3) to highlight critical studies conducted in keratoconus, laser refractive surgery, and glaucoma in order to aid interpretation of biomechanical parameters in the laboratory and in the clinic. A literature review was first conducted of basic biomechanical studies related to ocular tissue. The subsequent review of ocular biomechanical studies was limited to those focusing on keratoconus, laser refractive surgery, or glaucoma using the only two commercially available devices that allow rapid assessment of biomechanical response in the clinic. Foundational studies on ocular biomechanics used a combination of computer modeling and destructive forces on ex-vivo tissues. The knowledge gained from these studies could not be directly translated to clinical research and practice until the introduction of non-contact tonometers that quantified the deformation response of the cornea to an air puff, which represents a non-destructive, clinically appropriate load. The corneal response includes a contribution from the sclera which may limit corneal deformation. Two commercial devices are available, the Ocular Response Analyzer which produces viscoelastic parameters with a customized load for each eye, and the Corvis ST which produces elastic parameters with a consistent load for every eye. Neither device produces the classic biomechanical properties reported in basic studies, but rather biomechanical deformation response parameters which require careful interpretation. Research using clinical tools has enriched our understanding of how ocular disease alters ocular biomechanics, as well as how ocular biomechanics may influence the pathophysiology of ocular disease and response to surgical intervention.
Topics: Humans; Keratoconus; Biomechanical Phenomena; Cornea; Glaucoma; Sclera; Tonometry, Ocular; Intraocular Pressure
PubMed: 36239188
DOI: 10.1080/02713683.2022.2125530 -
Journal of Autoimmunity Apr 2024Scleritis is a severe and painful ophthalmic disorder, in which a pathogenic role for collagen-directed autoimmunity was repeatedly suggested. We evaluated the presence...
Scleritis is a severe and painful ophthalmic disorder, in which a pathogenic role for collagen-directed autoimmunity was repeatedly suggested. We evaluated the presence of sclera-specific antibodies in a large cohort of patients with non-infectious scleritis. Therefore, we prospectively collected serum samples from 121 patients with non-infectious scleritis in a multicenter cohort study in the Netherlands. In addition, healthy (n = 39) and uveitis controls (n = 48) were included. Serum samples were tested for anti-native human type II collagen antibodies using a validated enzyme-linked immunosorbent assay (ELISA). Further, sclera-specific antibodies were determined using indirect immunofluorescence (IIF) on primate retinal/scleral cryosections. Lastly, human leukocyte antigen (HLA) typing was performed in 111 patients with scleritis. Anti-type II collagen antibodies were found in 13% of scleritis patients, in 10% of healthy controls and in 11% of uveitis controls (p = 0.91). A specific reaction to scleral nerve tissue on IIF was observed in 33% of patients with scleritis, which was higher than in healthy controls (11%; p = 0.01), but similar to uveitis controls (25%; p = 0.36). Reactivity to the scleral nerve tissue was significantly associated with earlier onset of scleritis (48 versus 56 years; p < 0.001), bilateral involvement (65% versus 42%; p = 0.01), and less frequent development of scleral necrosis (5% versus 22%; p = 0.02). HLA-B27 was found to be twice as prevalent in patients with scleritis (15.3%) compared to a healthy population (7.2%). In conclusion, scleral nerve autoantibody reactivity was more common in scleritis and uveitis patients in contrast to healthy controls. Further research is needed to characterize these scleral-nerve directed antibodies and assess their clinical value.
Topics: Animals; Humans; Autoimmunity; Cohort Studies; Sclera; Scleritis; Uveitis
PubMed: 38368769
DOI: 10.1016/j.jaut.2024.103178