Extracelluar Matrix Organization and Biomechanics of the Lamina Cribrosa and Peripapillary Sclera in Populations at High Risk for Primary Open Angle Glaucoma

原发性开角型青光眼高危人群筛板和视乳头周围巩膜的细胞外基质组织和生物力学

• 批准号: 9293031
• 负责人: Jonathan Pieter Vande Geest
• 金额: $ 6.46万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-09 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9293031
• 关键词: Extracelluar; Matrix; Organization; Biomechanics; Lamina

Project Summary 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.

项目总结

项目成果

A one-dimensional mixed porohyperelastic transport swelling finite element model with growth.

具有增长的一维混合多孔超弹性输运膨胀有限元模型。

• DOI: 10.1016/j.jmbbm.2013.04.019
• 发表时间: 2014
• 期刊: Journal of the mechanical behavior of biomedical materials
• 影响因子: 3.9
• 作者: Harper,JL;Simon,BR;VandeGeest,JP
• 通讯作者: VandeGeest,JP

A Subdomain Method for Mapping the Heterogeneous Mechanical Properties of the Human Posterior Sclera.

绘制人类后巩膜异质机械特性的子域方法。

• DOI: 10.3389/fbioe.2019.00129
• 发表时间: 2019
• 期刊: Frontiers in bioengineering and biotechnology
• 影响因子: 5.7
• 作者: Kollech,HirutG;Ayyalasomayajula,Avinash;Behkam,Reza;Tamimi,Ehab;Furdella,Kenneth;Drewry,Michelle;VandeGeest,JonathanP
• 通讯作者: VandeGeest,JonathanP

A porohyperelastic finite element model of the eye: the influence of stiffness and permeability on intraocular pressure and optic nerve head biomechanics.

• DOI: 10.1080/10255842.2015.1052417
• 发表时间: 2016
• 期刊: Computer methods in biomechanics and biomedical engineering
• 影响因子: 1.6
• 作者: Ayyalasomayajula A;Park RI;Simon BR;Vande Geest JP
• 通讯作者: Vande Geest JP