The proposed biomechanical studies continue our multi-disciplinary group's attempts to build an engineering-based characterization of the principal components of ONH susceptibility to glaucomatous damage. They test the following Hypotheses regarding the effects of intraocular pressure (IOP) within the first finite element models (FEMs) of the load-bearing connective tissues of the optic nerve head (ONH): 1) The distribution of stress (force/cross-sectional area) and strain (local deformation) within the lamina cribrosa and scleral canal of the normal ONH predicts the sites of connective tissue damage in early experimental glaucoma. 2) At all levels of IOP, stresses and strains within the remaining connective tissues of early and moderate glaucoma eyes are higher than in normal eyes. 3) Fixed deformation of the connective tissues underlies the onset and progression of glaucomatous cupping in early and moderate glaucoma ONH but is not significantly present in early and late ONH ischemia. 4) The ONH and peripapillary connective tissues of older eyes are less elastic than those of younger eyes. ? ? The Specific Aims and Objectives are: 1) To expand the resolution and accuracy of the existing continuum FEMs of normal and early glaucomatous ONH by introducing anisotropric, bi-axial material properties and voxel-based finite elements; 2) To extend the modeling to moderate glaucomatous damage; 3) To make measurements within the digital 3D geometries of normal, early and moderate glaucomatous, and early and late endothelin-treated, ischemic ONH so as to characterize and compare the 3D patterns of connective tissue damage; 4) To compare ONH connective tissue deformation and bi-axial posterior scleral material properties in young and old eyes. ? ? The Methodology includes compliance testing of the ONH surface; bi-axial tensile testing of the intact posterior scleral shell; construction of digital 3D geometries of the ONH connective tissues from serial color images of the embedded tissue block surface after serial 3-um sectioning; and continuum, micro finite element, and hybrid finite element modeling of the load-bearing connective tissues of the ONH.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
3R01EY011610-09S1
Application #
7235458
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Liberman, Ellen S
Project Start
1998-07-01
Project End
2007-06-30
Budget Start
2005-12-28
Budget End
2006-06-30
Support Year
9
Fiscal Year
2006
Total Cost
$150,520
Indirect Cost
Name
Emanuel Hospital and Health Center
Department
Type
DUNS #
050973098
City
Portland
State
OR
Country
United States
Zip Code
97232
Yang, Hongli; Reynaud, Juan; Lockwood, Howard et al. (2018) 3D Histomorphometric Reconstruction and Quantification of the Optic Nerve Head Connective Tissues. Methods Mol Biol 1695:207-267
Yang, Hongli; Reynaud, Juan; Lockwood, Howard et al. (2017) The connective tissue phenotype of glaucomatous cupping in the monkey eye - Clinical and research implications. Prog Retin Eye Res 59:1-52
Wilsey, Laura; Gowrisankaran, Sowjanya; Cull, Grant et al. (2017) Comparing three different modes of electroretinography in experimental glaucoma: diagnostic performance and correlation to structure. Doc Ophthalmol 134:111-128
Stowell, Cheri; Burgoyne, Claude F; Tamm, Ernst R et al. (2017) Biomechanical aspects of axonal damage in glaucoma: A brief review. Exp Eye Res 157:13-19
Wilsey, Laura J; Reynaud, Juan; Cull, Grant et al. (2016) Macular Structure and Function in Nonhuman Primate Experimental Glaucoma. Invest Ophthalmol Vis Sci 57:1892-900
Ing, Eliesa; Ivers, Kevin M; Yang, Hongli et al. (2016) Cupping in the Monkey Optic Nerve Transection Model Consists of Prelaminar Tissue Thinning in the Absence of Posterior Laminar Deformation. Invest Ophthalmol Vis Sci 57:2914–2927
Fortune, Brad; Hardin, Christy; Reynaud, Juan et al. (2016) Comparing Optic Nerve Head Rim Width, Rim Area, and Peripapillary Retinal Nerve Fiber Layer Thickness to Axon Count in Experimental Glaucoma. Invest Ophthalmol Vis Sci 57:OCT404-12
Fortune, Brad; Reynaud, Juan; Hardin, Christy et al. (2016) Experimental Glaucoma Causes Optic Nerve Head Neural Rim Tissue Compression: A Potentially Important Mechanism of Axon Injury. Invest Ophthalmol Vis Sci 57:4403-11
Ivers, Kevin M; Yang, Hongli; Gardiner, Stuart K et al. (2016) In Vivo Detection of Laminar and Peripapillary Scleral Hypercompliance in Early Monkey Experimental Glaucoma. Invest Ophthalmol Vis Sci 57:OCT388-403
Reynaud, Juan; Lockwood, Howard; Gardiner, Stuart K et al. (2016) Lamina Cribrosa Microarchitecture in Monkey Early Experimental Glaucoma: Global Change. Invest Ophthalmol Vis Sci 57:3451-69

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