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.

Shear stress-induced atherosclerotic plaque composition in ApoE(-/-) mice is modulated by connexin37.

OBJECTIVE: Shear stress patterns influence atherogenesis and plaque stability; low laminar shear stress (LLSS) promotes unstable plaques whereas oscillatory shear stress (OSS) induces more stable plaques. Endothelial connexin37 (Cx37) expression is also regulated by shear stress, which may contribute to localization of atherosclerotic disease. Moreover, Cx37 reduces initiation of atherosclerosis by inhibiting monocyte adhesion. The present work investigates the effect of Cx37 on the phenotype of plaques induced by LLSS or OSS. METHODS: Shear stress-modifying casts were placed around the common carotid artery of ApoE(-/-) or ApoE(-/-)Cx37(-/-) mice, and animals were placed on a high-cholesterol diet for 6 or 9 weeks. Atherosclerotic plaque size and composition were assessed by immunohistochemistry. RESULTS: Plaque size in response to OSS was increased in ApoE(-/-)Cx37(-/-) mice compared to ApoE(-/-) animals. Most plaques contained high lipid and macrophage content and a low amount of collagen. In ApoE(-/-) mice, macrophages were more prominent in LLSS than OSS plaques. This difference was reversed in ApoE(-/-)Cx37(-/-) animals, with a predominance of macrophages in OSS plaques. The increase in macrophage content in ApoE(-/-)Cx37(-/-) OSS plaques was mainly due to increased accumulation of M1 and Mox macrophage subtypes. Cx37 expression in macrophages did not affect their proliferation or their polarization in vitro. CONCLUSION: Cx37 deletion increased the size of atherosclerotic lesions in OSS regions and abrogated the development of a stable plaque phenotype under OSS in ApoE(-/-) mice. Hence, local hemodynamic factors may modify the risk for adverse atherosclerotic disease outcomes associated to a polymorphism in the human Cx37 gene.

Computational model of evolving lens capsule biomechanics following cataract-like surgery.

Cataract surgery is an invasive procedure whereby lens fibers are removed through a permanent central hole, or capsulorhexis, in the surrounding lens capsule and replaced with an artificial intraocular lens (IOL). Remnant lens epithelial cells subsequently transdifferentiate to a more contractile and synthetic wound-healing phenotype, which causes significant structural and mechanical adaptations of the residual lens capsule. The goal of this study is to present a computational model capable of capturing salient features of the biomechanical evolution of the lens capsule following cataract-like surgery. The model is shown to predict marked long-term increases in thickness and stiffness of the lens capsule nearest the edge of the capsulorhexis comparable to reported measurements. Such models represent a first step toward understanding better the long-term interactions between the residual lens capsule and implanted IOL, thus initiating a new paradigm for the design of improved IOLs, including those having an accommodative feature.

Ex vivo quantification of the time course of contractile loading of the porcine lens capsule after cataract-like surgery.

Cataract surgery is an invasive procedure that replaces the quasi-spherical native lens fibers with a flat prosthetic device, which initially reduces mechanical stress within the remnant lens capsule and, ultimately, leads to contraction of the capsule about the implant. Although resultant changes in geometry have been quantified previously, little is known about the loads associated with this contraction. We present a novel experimental culture device to quantify ex vivo the time course of increases in tension within the contracting lens capsule after cataract-like surgery. Results demonstrate that contraction reaches steady state within approximately one month with a mean tension of 1.45 mN/mm and Cauchy (true) stress of 13.4 kPa. A significant increase in alpha-smooth muscle actin (alpha-SMA) was also found in post-cultured compared to fresh lens capsules, thus suggesting that transdifferentiated lens epithelial cells (LECs) modulated the contraction. Quantification of loads imparted by the contracting lens capsule is important for assessing implant/capsule interactions and implant stability in vivo. Because contraction of the capsule may be modulated in part by LECs attempting to restore their native mechanical environment, our results further suggest a possible mechanism for the long-term errant changes in capsular structure commonly observed after surgery.

Altered mechanical behavior and properties of the human anterior lens capsule after cataract surgery.

Several studies have quantified the mechanics of the normal lens capsule, motivated in large part by the need to understand better the mechanism of accommodation. In addition to this principal physiologic function, the lens capsule also plays a significant clinical role by housing the prosthetic lens implanted during cataract surgery. This procedure alters dramatically the mechanical environment of the capsule, which may modulate the errant behavior of lens epithelial cells that leads to capsular contraction and deposition of non-native matrix proteins. Although much is known about histological alterations within the post-surgical capsule, little is known about the altered mechanics. We performed uniaxial mechanical tests on normal and post-surgical human anterior lens capsules and found, for the first time, that cataract surgery leads to a significant stiffening of the capsule nearest the capsulorhexis edge. These data promise to be important for developing predictive tools capable of elucidating interactions between the post-surgical capsule and implant.

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.

Regional multiaxial mechanical properties of the porcine anterior lens capsule.

The lens capsule of the eye plays fundamental biomechanical roles in both normal physiological processes and clinical interventions. There has been modest attention given to the mechanical properties of this important membrane, however, and prior studies have focused on 1-D analyses of the data. We present results that suggest that the porcine anterior lens capsule has a complex, regionally dependent, nonlinear, anisotropic behavior. Specifically, using a subdomain inverse finite element method to analyze data collected via a new biplane video-based test system, we found that the lens capsule is nearly isotropic (in-plane) near the pole but progressively stiffer in the circumferential compared to the meridional direction as one approaches the equator. Because the porcine capsule is a good model of the young human capsule, there is strong motivation to determine if similar regional variations exist in the human lens capsule for knowledge of such complexities may allow us to improve the design of surgical procedures and implants.

Altered multiaxial mechanical properties of the porcine anterior lens capsule cultured in high glucose.

Hyperglycemia can alter the mechanical properties of tissues through the formation of advanced glycation endproducts in matrix proteins that have long half-lives. We used a custom experimental system and subdomain finite element method to quantify alterations in the regional multiaxial mechanical properties of porcine lens capsules that were cultured for 8 or 14 weeks in high glucose versus control media. Findings revealed that high glucose significantly stiffened the capsules in both the circumferential and the meridional directions, but it did not affect the known regional variations in anisotropy. Such information could be important in the design of both improved clinical procedures and intraocular implants for diabetic patients.

Redistribution of strain and curvature in the porcine anterior lens capsule following a continuous circular capsulorhexis.

Cataract surgery is the most commonly performed surgical procedure in the US, it consists of three steps: introduction of a hole into the lens capsule, removal of the clouded lens through this access hole, and insertion of an artificial lens. We hypothesize that errant behavior by the residual epithelial cells of the lens capsule following surgery are due, in part, to surgically-induced changes of the native stress and strain fields in the lens capsule. Because the capsular bag can be regarded mechanically as a membrane, here we study changes in curvature and strains due to the most common means of introducing the initial access hole: a continuous circular capsulorhexis (CCC). We show that a modest sized CCC increases circumferential strains and decreases meridional strains by up to approximately 20% and that curvatures change by up to approximately 13%, particularly near the edge of the CCC. We submit that such changes can induce mechanobiological responses that are responsible, in part, for some of the long-term complications following cataract surgery.

Multiaxial mechanical behavior of the porcine anterior lens capsule.

The biomechanics of the lens capsule of the eye is important both in physiologic processes such as accommodation and clinical treatments such as cataract surgery. Although the lens capsule experiences multiaxial stresses in vivo, there have been no measurements of its multiaxial properties or possible regional heterogeneities. Rather all prior mechanical data have come from 1-D pressure-volume or uniaxial force-length tests. Here, we report a new experimental approach to study in situ the regional, multiaxial mechanical behavior of the lens capsule. Moreover, we report multiaxial data suggesting that the porcine anterior lens capsule exhibits a typical nonlinear pseudo-elastic behavior over finite strains, that the in situ state is pre-stressed multi-axially, and that the meridional and circumferential directions are principal directions of strain, which is nearly equi-biaxial at the pole but less so towards the equator. Such data are fundamental to much needed constitutive formulations.