Abstract
Purpose: :
Trabecular meshwork (TM) cells produce CLANs when exposed to dexamethasone (DEX). TM cells within the untreated whole tissue also contain CLANs, and the proportion of CLANs appears to be elevated in cases of glaucoma. Our working hypothesis is that the presence of CLANs in TM cells increases their rigidity resulting reduction of their contractile ability which will ultimately impair the aqueous outflow. In this study we propose to investigate the effect of CLANs on the cells rigidity and on their ability to contract by using biomechanical finite element (FE) modeling of CLANs.
Methods: :
The actin within TM cells were imaged using a confocal microscope. The digital images were analyzed using Image J (open source) image analysis software. Normal stress fibers and CLANs within TM cells were analyzed to determine their physical dimensions in terms of actin fiber length and thickness, and the relative location of hub points. This information together with their physical properties reported in the literature was used to build a 2D FE model with the use of commercial software Abaqus (6.4). 3D CLANs were modeled as geodesic-domes and foreshortened domes (1/3rd the height). During our experiments we applied a variety of different forces, in order to understand the differences in their behavior.
Results: :
The 2D model was tested by applying the forces, at various locations, magnitudes and orientations. A range of mechanical boundary conditions were applied (e.g., constraints on the hubs). For comparison, we also build a synthesized stress fiber model which occupied the same area with the same physical properties. Under identical conditions, our results demonstrated at least a 10% reduction in the deformation of a CLAN structure compared to the corresponding stress fiber model. The 3D domes were cross compared (identical test conditions) under a variety of shearing forces. The displacement of the foreshortened dome was reduced by more than 40% compared to the full dome, and the resulting stress on the structure was reduced by over 20%.
Conclusions: :
As CLANs tend to be shallow structures, our model supports the theory of the introduction of increased rigidity. Our results are the first demonstration that CLANs are associated with increased rigidity of cells and also show that biomechanical FE modeling provides us with a powerful tool to study important cellular structures such as CLANs which are difficult for an in-vivo experiment. This will offer us improved knowledge of CLANs and their influence on the TM cell that may be of importance for the development of new treatment options.
Keywords: outflow: trabecular meshwork • cytoskeleton • computational modeling