September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
A Microstructure Based Model of Lamina Cribrosa Mechanical Insult under IOP
Author Affiliations & Notes
  • Andrew P Voorhees
    Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Ning-Jiun Jan
    Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
    Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • John G Flanagan
    Optometry and Vision Science, University of California Berkeley, Berkeley, California, United States
  • Jeremy M Sivak
    Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada
  • Ian A Sigal
    Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
    Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Andrew Voorhees, None; Ning-Jiun Jan, None; John Flanagan, None; Jeremy Sivak, None; Ian Sigal, None
  • Footnotes
    Support  NIH T32-EY017271, NIH R01 EY023966, NIH P30-EY008098, CIHR MOP123448, The Eye and Ear Foundation (Pittsburgh, PA)
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Andrew P Voorhees, Ning-Jiun Jan, John G Flanagan, Jeremy M Sivak, Ian A Sigal; A Microstructure Based Model of Lamina Cribrosa Mechanical Insult under IOP. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : It has been hypothesized that IOP-related mechanical insult within the lamina cribrosa (LC) may contribute to retinal ganglion cell (RGC) axon damage and glaucoma. To date, no models describe how mechanical stretch of RGC axons differs from the stretch of whole LC. We developed two models, a simplified homogeneous model (HM) and a specimen-specific, microstructure-based model (µM) using high-resolution microscopy data. The µM included the mechanics of neural tissue and captured the non-linearity, anisotropy, and inhomogeneity of the LC beams and sclera with detail that previous models have not.

Methods : A 30 μm thick section of a sheep optic nerve head was imaged using polarized light microscopy, and a small temporal region of the LC and sclera was modeled (Fig. 1). For µM, material properties were assigned according to the observed architecture, whereas HM had homogenized sclera and LC regions. We simulated a 2% scleral canal expansion, corresponding to a 5 mmHg increase in IOP. Only central regions of the models were analyzed to avoid edge effects.

Results : In HM, maximum stretch was 3% and occurred at the peripheral LC (Fig 2A). Stresses in the LC of HM were highly uniform. In µM, stretch varied greatly from pore to pore, with mean stretch in some pores more than 3 times that in neighboring pores and sometimes exceeding 30% (Fig 2C). Stresses were concentrated in the collagen beams (Fig 2D).

Conclusions : Our µM demonstrates that small changes in IOP can cause large deformations in RGC axons. Our model predicts large pore-to-pore variance in stretch, agreeing with recent experimental findings. This phenomenon is not explained by previous models. Microstructural aware modeling improves our understanding of how neural tissues suffer mechanical insult due to elevated IOP.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

Collagen fiber density and orientation were determined using polarized light microscopy. This data was used to generate a highly detailed finite element model with non-linear and anisotropic mechanical behavior. Only the bottom half of the model is shown to show the beam structure.

Collagen fiber density and orientation were determined using polarized light microscopy. This data was used to generate a highly detailed finite element model with non-linear and anisotropic mechanical behavior. Only the bottom half of the model is shown to show the beam structure.

 

A) The HM LC shows a low variation in stretch. B) Tensile stretch in the µM varied greatly from pore to pore. C) The distribution of tensile stretch in the neural tissue (red) had a larger median and variance as compared to the beams (blue) and the homogenous LC (magenta). D) High stresses are seen in LC beams.

A) The HM LC shows a low variation in stretch. B) Tensile stretch in the µM varied greatly from pore to pore. C) The distribution of tensile stretch in the neural tissue (red) had a larger median and variance as compared to the beams (blue) and the homogenous LC (magenta). D) High stresses are seen in LC beams.

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