Glaucoma is the 2nd leading cause of blindness worldwide, as 7 million people are blind from this condition. There have been extensive studies concluding that primary open angle glaucoma (POAG) has a higher prevalence in populations of both African descent and Hispanic ethnicity. The mechanical theory of glaucoma rests on the assumption that mechanical damage forces acting on the optic nerve cause a loss of retinal ganglion cell function. While there is evidence that the extracellular matrix of the lamina cribrosa (LC) and peripapillary sclera (PS) remodel in the presence of glaucoma, this remodeling has not been extensively quantified in certain higher risk populations (aged, African Descent (AD), Hispanic Ethnicity (HE)). Preferential differences in the PS microstructure and mechanical properties of these populations may provide a mechanism by which POAG can occur at normal IOPs. The current research proposal will investigate the relationship between PS and LC matrix microstructure and mechanical properties, seeking to identify how these relationships are affected by race/ethnicity and age. The central hypothesis of the proposed work is that differences in the microstructure and mechanical properties of the LC and PS exist as a function of race/ethnicity and age. These changes are hypothesized to play a role in the higher prevalence of glaucoma in populations of AD and HE compared with those of European Descent (ED), independent of the level of intraocular pressure. While the extracellular matrix microstructures of the LC and PS have been investigated previously, how such organization relates to the mechanical function of these tissues is not currently understood. This is primarily due to the fact that nearly all quantification of this microstructural information has resulted from histological studies which rely on snap freezing or fixing the tissue in an embedding medium (thus precluding simultaneous mechanical characterization). We have recently developed a micro-optomechanical (MOMD) device which is capable of simultaneously measuring the matrix organization of unfixed LC and PS while these tissues undergo mechanical deformations. The MOMD excites the second harmonic generation of collagen and the two-photon emitted fluorescence of elastin while simultaneously exposing posterior ocular tissues to either planar biaxial or pressure-inflation loads. The three primary aims of this project are to identify differences (as a function of race/ethnicity and age) in 1) the microstructural organization of the human LC at various IOPs; 2) the biomechanical response and microstructure the human PS at various IOPs;and 3) the biomechanical environment of posterior ocular tissues using microstructurally-based computational simulations. Providing a detailed account of age and ethnicity associated differences in LC and PS microstructure and mechanical properties may provide a unique opportunity for the development of novel diagnosis and treatment opportunities.

Public Health Relevance

As the second leading cause of blindness worldwide, glaucoma is estimated to affect 60 million people in 2010 and will affect 80 million by 2020. Alterations in the makeup and properties of the tissues near the optic nerve may predispose certain high risk populations to primary open angle glaucoma, even at relatively low intraocular pressures. Identification of such changes may eventually lead to improved diagnosis and treatment of this disease.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Anterior Eye Disease Study Section (AED)
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Chin, Hemin R
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University of Arizona
Engineering (All Types)
Schools of Engineering
United States
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Ram, Sundaresh; Danford, Forest; Howerton, Stephen et al. (2018) Three-Dimensional Segmentation of the Ex-Vivo Anterior Lamina Cribrosa From Second-Harmonic Imaging Microscopy. IEEE Trans Biomed Eng 65:1617-1629
Tamimi, Ehab A; Pyne, Jeffrey D; Muli, Dominic K et al. (2017) Racioethnic Differences in Human Posterior Scleral and Optic Nerve Stump Deformation. Invest Ophthalmol Vis Sci 58:4235-4246
Armstrong, Michelle Hine; Buganza Tepole, Adrián; Kuhl, Ellen et al. (2016) A Finite Element Model for Mixed Porohyperelasticity with Transport, Swelling, and Growth. PLoS One 11:e0152806
Haskett, Darren G; Maestas, David; Howerton, Stephen J et al. (2016) 2-Photon Characterization of Optical Proteolytic Beacons for Imaging Changes in Matrix-Metalloprotease Activity in a Mouse Model of Aneurysm. Microsc Microanal 22:349-60
Ayyalasomayajula, Avinash; Park, Robert I; Simon, Bruce R et al. (2016) A porohyperelastic finite element model of the eye: the influence of stiffness and permeability on intraocular pressure and optic nerve head biomechanics. Comput Methods Biomech Biomed Engin 19:591-602
Pyne, Jeffrey D; Genovese, Katia; Casaletto, Luciana et al. (2014) Sequential-digital image correlation for mapping human posterior sclera and optic nerve head deformation. J Biomech Eng 136:021002
Harper, J L; Simon, B R; Vande Geest, J P (2014) A one-dimensional mixed porohyperelastic transport swelling finite element model with growth. J Mech Behav Biomed Mater 29:663-75
Danford, Forest L; Yan, Dongmei; Dreier, Robert A et al. (2013) Differences in the region- and depth-dependent microstructural organization in normal versus glaucomatous human posterior sclerae. Invest Ophthalmol Vis Sci 54:7922-32
Keyes, Joseph T; Yan, Dongmei; Rader, Jacob H et al. (2011) A gimbal-mounted pressurization chamber for macroscopic and microscopic assessment of ocular tissues. J Biomech Eng 133:095001