The proposed biomechanical studies test the following hypotheses regarding the effects of intraocular pressure (IOP) within the load bearing connective tissues of the optic nerve head (ONH): 1) The lamina cribrosa and scleral canal of the normal ONH deform under the effects of an acute increase in IOP related stress (force/cross-sectional area). 2) An increase in this deformation underlies the onset of ONH surface hypercompliance in experimental glaucoma. 3) The magnitude of IOP-related stress within the ONH connective tissues is substantial at all levels of IOP. and, 4) for a given level of IOP, the magnitude of IOP-related stress is principally influenced by the size, shape, and three-dimensional (3-D) anatomy of the scleral canal.
The specific aims are : 1) to measure and compare the position of the lamina cribrosa and scleral canal diameter within serial Sagittal and transverse sections of both eyes of normal monkeys in which one eye was perfusion fixed at low and the other at high IOP; 2) to make similar comparisons between both eyes of a monkey after one ONH has been made hypercompliant by the induction of unilateral experimental glaucoma; and 3) to build and test a series of finite element models (FEMs) of the load bearing connective tissues of the normal and hypercompliant monkey ONH so as to characterize the distribution and magnitude of IOP-related stress. The stress-strain testing of posterior monkey sclera to determine its viscoelastic material properties. The methodology includes compliance testing of the ONH (to detect the onset of hypercompliance in experimental glaucoma); uniaxial stress-strain testing (to determine the material properties of posterior sclera); 3-D reconstruction of digitized histologic sections (to construct the first digital, 3-D geometry's of the ONH load bearing tissues at physiologic and pathophysiologic levels of IOP); and finite element modeling of the load bearing tissues of the ONH to characterize the distribution of IOP-related stress within the ONH. These studies lay the foundation for the clinical estimation of an individual patient's susceptibility to glaucomatous damage at a given level of IOP.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Visual Sciences A Study Section (VISA)
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Liberman, Ellen S
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Louisiana State University Hsc New Orleans
Schools of Medicine
New Orleans
United States
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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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