Abstract
Purpose :
The iris stroma in patients with a history of primary angle-closure glaucoma (PACG) is known to contain more collagen and be mechanically stiffer than that of healthy individual. Since in many types of cells, nuclear deformation is involved in collagen gene expression and protein synthesis, the purpose of this study was to identify how the nuclear shape in iris stromal cells alters with pupillary responses.
Methods :
A three-dimensional (3-D) multi-scale finite-element (FE) model of the iris was generated based on the quantified microstructural parameters using small angle light scattering technique. The model was verified using experimental porcine data (Exp Eye Res, 89: 456-461). Miosis was simulated by assigning an active muscle contractile stress to the sphincter region of the iris. Incompressible 3-D ellipsoids with an average nuclear aspect ratio (NAR) of 2.0 were considered as the initial stromal cell nuclei. We then computed the deformed nuclear shapes based on the predicted extracellular matrix (ECM) deformation. The simulations were performed on an HP Intel Xeon machine at the Ohio Supercomputing Center (Columbus, OH).
Results :
When the pupil diameter constricted from 6.3 mm to 5.1 mm, the NAR value of the nuclei—initially aligned with the main direction of the ECM fibers—increased from 2.0 to 2.63 (Fig. 1). The changes in the NAR values eventually decreased with deformation as the ECM fibers became less crimped.
Conclusions :
Nuclear configuration, closely linked to ECM fiber architecture, varies in response to miosis. Our multi-scale modeling approach will help us understand the relationship between iris stiffening and iris stromal cell nuclear deformation, potentially providing mechanistic clues of why the iris may become stiffer in certain angle-closure suspects and PACG patients.
This is a 2020 ARVO Annual Meeting abstract.