Biomechanics of the Lens Capsule from Native to After Cataract Surgery

The primary function of the lens capsule of the eye unfolds during the process of accommodation; wherein, tension imposed onto its equator is released, allowing the elastic capsule to mold the underlying lens nucleus and cortex into a more quasispherical morphology to change focus from distant to near objects. Given its highly mechanical nature, it is prudent to study the native lens capsule from the perspective of biomechanics for such applications as understanding the mechanism of accommodation. Further, cataract surgery introduces alterations to the geometry of the lens capsule that lead to changes in resident cell behavior from quiescent to contractile and synthetic. Though resultant changes in capsule histology are well documented little has been done to quantify the corresponding altered mechanics, which is important for elucidating related post-surgical pathologies and improving prosthetic lens design. In this study we present the first data on the in situ multiaxial mechanical behavior of the native and hyperglycemic anterior lens capsule in both the porcine and human models. From these data, native stresses in the lens capsule are calculated using a finite element analysis, and alterations in the corresponding strain field are calculated after the introduction of a continuous circular capsulorhexis, which is imposed during cataract surgery. Finally, we quantify both the altered mechanical behavior and contractile loads imposed onto the lens capsule after cataract surgery

Perturbed Stress Field of the Human Lens Capsule After Cataract Surgery

Current modeling of the human lens capsule has been focused on the mechanism of accommodation and its decline with age, but few studies have modeled the effects of cataract surgery and quantified the altered mechanical environment introduced by the procedure. The goal of this study is to develop the first fully 3-D finite element model of the post-surgical human lens capsule with an implanted device in order to characterize lens capsule mechanics after cataract surgery. The model demonstrates a highly perturbed stress field compared to the native state, which we hypothesize is the primary driving force behind the long-term errant cell behavior that causes secondary cataracts. Such predict capabilities may lend insight on future intraocular lens designs, potentially ones that can restore youthful accommodation

Accommodation of the human lens capsule using a finite element model based on nonlinear regionally anisotropic biomembranes

Accommodation of the eyes, the mechanism that allows humans to focus their vision on near objects, naturally diminishes with age via presbyopia. People who have undergone cataract surgery, using current surgical methods and artificial lens implants, are also left without the ability to accommodate. The process of accommodation is generally well known; however the specific mechanical details have not been adequately explained due to difficulties and consequences of performing in vivo studies. Most studies have modeled the mechanics of accommodation under assumptions of a linearly elastic, isotropic, homogenous lens and lens capsule. Recent experimental and numerical studies showed that the lens capsule exhibits nonlinear elasticity and regional anisotropy. In this paper we present a numerical model of human accommodation using a membrane theory based finite element approach, incorporating recent findings on capsular properties. This study seeks to provide a novel perspective of the mechanics of accommodation. Such findings may prove significant in seeking biomedical solutions to restoring loss of visual power

Implantation of a capsular tension ring during cataract surgery attenuates predicted remodeling of the post-surgical lens capsule along the visual axis

Introduction: Cataract surgery permanently alters the mechanical environment of the lens capsule by placing a hole in the anterior portion and implanting an intraocular lens (IOL) that has a very different geometry from the native lens. We hypothesized that implant configuration and mechanical interactions with the post-surgical lens capsule play a key role in determining long-term fibrotic remodeling. Methods: We developed the first finite element-growth and remodeling (FE-G&R) model of the post-surgical lens capsule to evaluate how implantation of an IOL with and without a capsular tension ring (CTR) impacted evolving lens capsule mechanics and associated fibrosis over time after cataract surgery. Results: Our models predicted that implantation of a CTR with the IOL into the post-surgical lens capsule reduced the mechanical perturbation, thickening, and stiffening along the visual axis in both the remnant anterior and posterior portions compared to implantation of the IOL alone. Discussion: These findings align with patient studies and suggest that implantation of a CTR with the IOL during routine cataract surgery would attenuate the incidence of visually-debilitating capsule fibrosis. Our work demonstrates that use of such modeling techniques has substantial potential to aid in the design of better surgical strategies and implants

Regional mechanical properties and stress analysis of the human anterior lens capsule

The lens capsule of the eye functions, in part, as a deformable support through which the ciliary body applies tractions that can alter lens curvature and corresponding refractive power during the process of accommodation. Although it has long been recognized that characterization of the mechanical properties of the lens capsule is fundamental to understanding this physiologic process as well as clinical interventions, prior data have been limited by one-dimensional testing of excised specimens despite the existence of multiaxial loading in vivo. In this paper, we employ a novel experimental approach to study in situ the regional, multiaxial mechanical behavior of both normal and diabetic human anterior lens capsules. Furthermore, we use these data to calculate material parameters in a nonlinear stress– strain relation via a custom sub-domain inverse finite element method (FEM). These parameters are then used to predict capsular stresses in response to imposed loads using a forward FEM model. Our results for both normal and diabetic human eyes show that the anterior lens capsule exhibits a nonlinear pseudoelastic behavior over finite strains that is typical of soft tissues, and that strains are principal relative to meridional and circumferential directions. Experimental data and parameter estimation suggest further that the capsule is regionally anisotropic, with the circumferential direction becoming increasingly stiffer than the meridional direction towards the equator. Although both normal and diabetic lens capsules exhibited these general characteristic behaviors, diabetic capsules were significantly stiffer at each distension. Finally, the forward FEM model predicted a nearly uniform, equibiaxial stress field during normalcy that will be perturbed by cataract surgery. Such mechanical perturbations may be an underlying modulator of the sustained errant epithelial cell behavior that is observed well after cataract surgery and may ultimately contribute to opacification of the posterior lens capsule

Implantation of a capsular tension ring during cataract surgery attenuates predicted remodeling of the post-surgical lens capsule along the visual axis

Introduction: Cataract surgery permanently alters the mechanical environment of the lens capsule by placing a hole in the anterior portion and implanting an intraocular lens (IOL) that has a very different geometry from the native lens. We hypothesized that implant configuration and mechanical interactions with the post-surgical lens capsule play a key role in determining long-term fibrotic remodeling.Methods: We developed the first finite element-growth and remodeling (FE-G&R) model of the post-surgical lens capsule to evaluate how implantation of an IOL with and without a capsular tension ring (CTR) impacted evolving lens capsule mechanics and associated fibrosis over time after cataract surgery.Results: Our models predicted that implantation of a CTR with the IOL into the post-surgical lens capsule reduced the mechanical perturbation, thickening, and stiffening along the visual axis in both the remnant anterior and posterior portions compared to implantation of the IOL alone.Discussion: These findings align with patient studies and suggest that implantation of a CTR with the IOL during routine cataract surgery would attenuate the incidence of visually-debilitating capsule fibrosis. Our work demonstrates that use of such modeling techniques has substantial potential to aid in the design of better surgical strategies and implants

In Vitro Models for Glaucoma Research: Effects of Hydrostatic Pressure

PURPOSE. The response of cells (e.g., optic nerve head [ONH] cells) to mechanical stress is important in glaucoma. Studies have reported the biological effects of hydrostatic pressure on ONH cells cultured on a rigid substrate. An apparatus, designed to independently vary hydrostatic pressure and gas tension (including oxygen tension) in culture medium, was used to evaluate the effects of pressure and tension on cell migration, shape, and α-tubulin architecture in a transformed cell line (DITNC1 rat cortical astrocytes). METHODS. During the assay period, cells were exposed to one of four experimental configurations: (1) control pressure and control gas tension; (2) high-pressure (7.4 mm Hg) and reduced gas tension; (3) control pressure and reduced gas tension; and (4) high-pressure and control gas tension. RESULTS. Calculations suggested that the cells in configurations 2 and 3 were hypoxic, as confirmed by direct measurements in configuration 2. No effects of hydrostatic pressure were observed on cell migration or α-tubulin architecture. However, cells cultured under low gas tension (configurations 2 and 3) showed increased migration at 48 and 72 hours (P \u3c 0.05). CONCLUSIONS. A hydrostatic pressure of 7.4 mm Hg has no effect on DITNC1 astrocytes cultured on rigid coverslips, whereas hypoxia associated with a fluid column creating this pressure does. These results differ from those in a previous report, the results of which may be explained by altered gas tensions in the culture medium. Steps are recommended for control of secondary effects when testing the effect of pressure on cultured cells

Quantification of plaque stiffness by Brillouin microscopy in experimental thin cap fibroatheroma

Plaques vulnerable to rupture are characterized by a thin and stiff fibrous cap overlaying a soft lipid-rich necrotic core. The ability to measure local plaque stiffness directly to quantify plaque stress and predict rupture potential would be very attractive, but no current technology does so. This study seeks to validate the use of Brillouin microscopy to measure the Brillouin frequency shift, which is related to stiffness, within vulnerable plaques. The left carotid artery of an ApoE-/- mouse was instrumented with a cuff that induced vulnerable plaque development in nine weeks. Adjacent histological sections from the instrumented and control arteries were stained for either lipids or collagen content, or imaged with confocal Brillouin microscopy. Mean Brillouin frequency shift was 15.79±0.09 GHz in the plaque compared with 16.24±0.15 (p \u3c 0.002) and 17.16±0.56 GHz (p \u3c 0.002) in the media of the diseased and control vessel sections, respectively. In addition, frequency shift exhibited a strong inverse correlation with lipid area of 20.67±0.06 (p \u3c 0.01) and strong direct correlation with collagen area of 0.71±0.15 (p \u3c 0.05). This is the first study, to the best of our knowledge, to apply Brillouin spectroscopy to quantify atherosclerotic plaque stiffness, which motivates combining this technology with intravascular imaging to improve detection of vulnerable plaques in patients

Co-culture models of endothelial cells, macrophages, and vascular smooth muscle cells for the study of the natural history of atherosclerosis

Background This work aims to present a fast, affordable, and reproducible three-cell co-culture system that could represent the different cellular mechanisms of atherosclerosis, extending from atherogenesis to pathological intimal thickening. Methods and results We built four culture models: (i) Culture model #1 (representing normal arterial intima), where human coronary artery endothelial cells were added on top of Matrigel-coated collagen type I matrix, (ii) Culture model #2 (representing atherogenesis), which demonstrated the subendothelial accumulation and oxidative modification of low-density lipoproteins (LDL), (iii) Culture model #3 (representing intimal xanthomas), which demonstrated the monocyte adhesion to the endothelial cell monolayer, transmigration into the subendothelial space, and transformation to lipid-laden macrophages, (iv) Culture model #4 (representing pathological intimal thickening), which incorporated multiple layers of human coronary artery smooth muscle cells within the matrix. Coupling this model with different shear stress conditions revealed the effect of low shear stress on the oxidative modification of LDL and the upregulation of pro-inflammatory molecules and matrix-degrading enzymes. Using electron microscopy, immunofluorescence confocal microscopy, protein and mRNA quantification assays, we showed that the behaviors exhibited by the endothelial cells, macrophages and vascular smooth muscle cells in these models were very similar to those exhibited by these cell types in nascent and intermediate atherosclerotic plaques in humans. The preparation time of the cultures was 24 hours. Conclusion We present three-cell co-culture models of human atherosclerosis. These models have the potential to allow cost- and time-effective investigations of the mechanobiology of atherosclerosis and new anti-atherosclerotic drug therapies

Restoration of normal blood flow in atherosclerotic arteries promotes plaque stabilization

Blood flow is a key regulator of atherosclerosis. Disturbed blood flow promotes atherosclerotic plaque development, whereas normal blood flow protects against plaque development. We hypothesized that normal blood flow is also therapeutic, if it were able to be restored within atherosclerotic arteries. Apolipoprotein E-deficient (ApoE-/-) mice were initially instrumented with a blood flow-modifying cuff to induce plaque development and then five weeks later the cuffwas removed to allowrestoration of normal blood flow. Plaques in decuffed mice exhibited compositional changes that indicated increased stability compared to plaques in mice with the cuff maintained. The therapeutic benefit of decuffingwas comparable to atorvastatin and the combination had an additive effect. In addition, decuffing allowed restoration of lumen area, blood velocity, and wall shear stress to near baseline values, indicating restoration of normal blood flow. Our findings demonstrate that the mechanical effects of normal blood flow on atherosclerotic plaques promote stabilization