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Technical Brief

A Methodology for Individual-Specific Modeling of Rat Optic Nerve Head Biomechanics in Glaucoma

[+] Author and Article Information
Stephen A. Schwaner

George W. Woodruff School of Mechanical Engineering,
Georgia Institute of Technology,
315 Ferst Drive,
2306 IBB,
Atlanta, GA 30332
e-mail: sschwaner3@gatech.edu

Alison M. Kight

Coulter Department of Biomedical Engineering,
Georgia Institute of Technology/Emory University,
Atlanta, GA 30332
e-mail: akight3@gatech.edu

Robert N. Perry

Coulter Department of Biomedical Engineering,
Georgia Institute of Technology/Emory University,
Atlanta, GA 30332
e-mail: rperry36@gatech.edu

Marta Pazos

Institut Clínic d'Oftalmologia,
Hospital Clínic de Barcelona,
Barcelona 08036, Spain
e-mail: martapazoslopez@gmail.com

Hongli Yang

Optic Nerve Head Research Laboratory,
Discoveries in Sight Research Laboratories,
Devers Eye Institute, Legacy Health System,
Portland, OR 97210
e-mail: hyang@deverseye.org

Elaine C. Johnson

The Kenneth C. Swan Ocular Neurobiology Laboratory,
Casey Eye Institute,
Oregon Health and Science University,
Portland, OR 97239
e-mail: johnsoel@ohsu.edu

John C. Morrison

The Kenneth C. Swan Ocular Neurobiology Laboratory,
Casey Eye Institute,
Oregon Health and Science University,
Portland, OR 97239
e-mail: morrisoj@ohsu.edu

Claude F. Burgoyne

Optic Nerve Head Research Laboratory,
Discoveries in Sight Research Laboratories,
Devers Eye Institute,
Legacy Health System,
Portland, OR 97210
e-mail: cfburgoyne@deverseye.org

C. Ross Ethier

Coulter Department of Biomedical Engineering,
Georgia Institute of Technology/Emory University,
Atlanta, GA 30332
e-mail: ross.ethier@bme.gatech.edu

1Corresponding author.

Manuscript received January 1, 2018; final manuscript received April 10, 2018; published online May 24, 2018. Assoc. Editor: Rouzbeh Amini.

J Biomech Eng 140(8), 084501 (May 24, 2018) (10 pages) Paper No: BIO-18-1001; doi: 10.1115/1.4039998 History: Received January 01, 2018; Revised April 10, 2018

Glaucoma is the leading cause of irreversible blindness and involves the death of retinal ganglion cells (RGCs). Although biomechanics likely contributes to axonal injury within the optic nerve head (ONH), leading to RGC death, the pathways by which this occurs are not well understood. While rat models of glaucoma are well-suited for mechanistic studies, the anatomy of the rat ONH is different from the human, and the resulting differences in biomechanics have not been characterized. The aim of this study is to describe a methodology for building individual-specific finite element (FE) models of rat ONHs. This method was used to build three rat ONH FE models and compute the biomechanical environment within these ONHs. Initial results show that rat ONH strains are larger and more asymmetric than those seen in human ONH modeling studies. This method provides a framework for building additional models of normotensive and glaucomatous rat ONHs. Comparing model strain patterns with patterns of cellular response seen in studies using rat glaucoma models will help us to learn more about the link between biomechanics and glaucomatous cell death, which in turn may drive the development of novel therapies for glaucoma.

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Figures

Grahic Jump Location
Fig. 1

Histologic section of the rat (a) (modified from Ref. [45]) and schematic drawing of the human (b) ONH (modified from Ref. [51]) illustrating their anatomical differences, including five key differences of particular interest (1)-(5) as described in the text. Abbreviations: CRA (A) and CRV (V).

Grahic Jump Location
Fig. 2

Manual delineation of tissue boundaries: (a) Radial section through rat ONH with tissue boundaries delineated: BM, anterior scleral boundary, posterior scleral boundary, neural boundary, posterior pia mater outer boundary. (b) Transverse section normal to nerve axis with tissue boundaries delineated: CRV, CRA, IAC. (c) Point clouds produced from delineation of radial sections and cross sections.

Grahic Jump Location
Fig. 3

Overview of geometry building process. See text for abbreviations. (a)-(e) Point cloud and surface fit of (a) BM and sclera, (b) optic nerve, (c) CRA, (d) IAC, (e) CRV. (f) Intersecting tissue surfaces before Boolean operations were performed. (g) Superior-Inferior cut view of MR05OD model geometry. (h)-(p) Individual tissue volumes (not to scale): (h) BM, (i) choroid, (j) sclera, (k) optic nerve, (l) PNVP, (m) pia mater, (n) IAC, (o) CRV, and (p) CRA.

Grahic Jump Location
Fig. 4

Projection of model tissue outlines onto digital section to ensure accurate representation of individual-specific tissue geometry. Note that the “shadow-like” appearance in parts of the section is an artifact of the reconstruction process. It occurs because highly pigmented tissue within the semitransparent paraffin block can be seen even before it is cut by the microtome.

Grahic Jump Location
Fig. 5

Superior-Inferior cut plane view illustrating a match between individual-specific model geometry (opaque) with generic posterior eye geometry (semitransparent). Tissue colors are the same as in Fig. 3. Transparent red blocks on anterior choroid and posterior sclera are the very soft material used to interpolate displacement values to any protruding individual-specific model edges.

Grahic Jump Location
Fig. 6

Computed first and third principal strain patterns for three different rat ONH models: MR04OD (top left), MR05OD (top right), and MR10OS (bottom left). Superior (S), inferior (I), nasal (N), and temporal (T) directions are indicated. Top rows show en face view, middle rows show S-I cut view, and bottom rows show T-N cut view. Tissue colors are the same as in Fig. 3. All scale bars are 100 μm. All three models have primary strain concentrations along the inferior side of the anterior nerve. MR10OS and MR04OD have more prominent strain concentrations around the BM overhang edge than MR05OD. MR10OS has particularly high strain concentrations in the inferior nerve as seen from the en face view.

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