Abstract
Purpose :
The rat is widely used to study glaucoma. However, rat ONH anatomy differs from human, likely producing different biomechanics. Rat ONH biomechanics have not been characterized but are important to e.g. understand ONH astrocyte mechanobiology in glaucoma. Digital 3D histomorphometric reconstructions (Pazos+, EER, 2015 & in press) are now available to drive FE modeling. Here we describe a pipeline for creating the first FE models allowing determination of hard/impossible-to-measure rat ONH biomechanics under glaucomatous loading conditions.
Methods :
Following perfusion fixation, the following landmarks were manually delineated within 40 digital radial sections through a normotensive rat ONH reconstruction: neurovascular scleral canal, nerve, central retinal artery (CRA), central retinal vein (CRV), perineural vascular plexus (PNVP), and inferior arterial canal (IAC). From point clouds, we created solid tissue geometries for FE modeling in ABAQUS. Tissues were modeled as isotropic neo-Hookean materials with elastic moduli based on values from past human modeling studies (Sigal+, IOVS, 2004) and Poisson’s ratio = 0.49 to enforce near-incompressibility. IOP was applied to the anterior surface of the model, and venous and arterial blood pressures (BP) were applied to CRA and CRV lumens. Edge boundary conditions were applied via submodeling: a simplified posterior eye model was created/solved, and displacements from matching positions were applied to the scleral edges of a local model (Fig 1).
Results :
To establish proof-of-principle, we explored a range of IOP and BPs in a single ONH. Figure 2 shows exemplar results at IOP = 20 mmHg and arterial/venous BPs = 61/41 mmHg. ONH stresses and strains ranged widely, with 95th percentile values of 14.6 kPa and 23.3% (first principal stress and strain), exceeding those expected in human ONH at equivalent IOPs.
Conclusions :
This method for FE model construction of the rat ONH is a first step in understanding rat ONH biomechanics. Model enhancements, incorporating rat-specific tissue properties and modeling additional normal and hypertensive ONHs will allow us to study biomechanical effects of tissue architecture and map regional strain variations to biological outcomes. This will improve our understanding of axonal injury pathogenesis in glaucoma.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.