# Determinants of the Biomechanical Behavior of the Human Lamina Cribrosa

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $368,825

## Abstract

Project Abstract
Background: Optic nerve head (ONH) biomechanics is thought to play a critical role in the pathophysiology of
primary open angle glaucoma (POAG). ONH biomechanics is driven be the interactions between intraocular
pressure (IOP), cerebrospinal fluid pressure (CSFP) and connective tissue structural stiffness (the combination
of tissue architecture and material properties) in the ONH and sclera. Computational and experimental studies
in animal models have suggested that strain (tissue stretch) in the ONH microenvironment is strongly influenced
by the structural stiffness of the sclera and the morphology and density of the lamina cribrosa (LC). Experimental
studies have shown that these structures also vary with the development of glaucoma, with age and across racial
groups of African descent (AD) vs. European descent (ED) and may also be associated with variation in corneal
thickness and rigidity. This is important since age, glaucoma severity, AD and corneal thickness and rigidity are
the most consistent risk factors for OAG independent of IOP. The Objectives of this study are: 1) to discover
how the morphology of the LC and scleral rigidity determine the mechanical behavior of the ONH in response to
changes in IOP and CSFP and 2) to determine how differences in structural stiffness of the scleral, ONH and
cornea seen in aging, with glaucoma and across racial groups are related to ONH strain. Design: This study will
employ a novel resource, the Alabama Living Eye Project. This program affords access to brain-dead organ
donors prior to organ procurement. Follow discussion and consent with the next-of-kin, an ocular exam with
biometry will be performed, followed by the quantification of in-vivo ONH strain in response to changes in both
IOP and CSFP using spectral domain optical coherence tomography (SDOCT). Following organ procurement,
scleral structural stiffness will be measured with laser electronic speckle pattern interferometry and ONH
microstructure will be quantified in digital 3D histologic episcopic reconstructions of the ONH. Multivariable
models will be used to determine the impact of scleral rigidity and ONH morphology on ONH strain and if these
relationships differ in aged and glaucomatous eyes, in eyes from AD or ED donors and with variations in corneal
stiffness. Impact: This study provides the unique opportunity to link scleral and ONH biomechanics to clinical
ocular imaging and biometrics data, and will elucidate the causative mechanisms related to the variation in ONH
biomechanics seen with age, with glaucoma, across AD and ED groups and associated with measurement of
corneal thickness and rigidity. Not only will this information inform the development of mechanistically relevant
biomarkers for glaucoma susceptibility, understanding how scleral stiffness and ONH morphology modulate ONH
biomechanics will guide the development of new non-IOP lowering glaucoma therapies targeted at altering
strain-driven remodeling of t...

## Key facts

- **NIH application ID:** 9997935
- **Project number:** 5R01EY028284-03
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Massimo Antonio Fazio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $368,825
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997935

## Citation

> US National Institutes of Health, RePORTER application 9997935, Determinants of the Biomechanical Behavior of the Human Lamina Cribrosa (5R01EY028284-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9997935. Licensed CC0.

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