Optic nerve head microstructure, biomechanics and susceptibility to glaucoma

描述(申请人提供)：通过开发一种基于青光眼结构评估青光眼风险的技术，以及对导致神经组织退化的机制有更深入的了解，早期青光眼的检测和治疗将得到极大的提高。我们的目标是确定眼睛的特性，在它发生之前预测神经组织损伤的易感性。早期青光眼神经组织变性通常局限于视神经头(ONH)的特定区域，年龄增长和眼压(IOP)升高增加了发生青光眼的风险。我们的中心假设是，ONH的结缔组织的结构，特别是内部筛板的结构，决定了局部对IOP的稳健性和敏感性，并由此决定了局部 早期青光眼对神经组织损伤的易感性。我们开发了新的成像技术来获得以前无法获得的ONH组织的微米级信息，包括胶原纤维排列和纤维的拉伸或松弛程度的详细地图，称为卷曲。有了这些信息，我们非常详细地描述了体系结构 在眼压正常和升高的情况下，对人体筛板及其周围组织进行观察。在目标1中，我们测试了早期青光眼对神经组织损伤的区域易感性与组织结构之间存在关联的预测。在目标2中，我们测试了这样的预测，即已知的青光眼早期损害易感区域对高眼压更敏感，因为这些区域的板层小梁中的胶原纤维最先伸展。 当眼压升高时，所有卷曲都会消失。我们还测试了这样的假设，即衰老与组织结构的变化有关，因此年长的眼睛不如年轻的眼睛强壮。在目标3中，我们使用数值模拟来确定年龄与组织结构和对IOP的敏感性之间的功能关系，并检验以下假设：筛板和乳突周围巩膜的结构是局部对IOP敏感性的主要决定因素，以及与年龄相关的组织结构变化增加了对IOP的敏感性。这个项目将产生迄今为止最详细的对 ONH的组织及其随年龄的变化。我们将开发一个全面的模型，以了解决定局部眼压敏感性的结构要素，并确定与早期青光眼神经组织损伤的局部敏感性相关的ONH结构特征。这一特征将跨越多个尺度，从胶原纤维的非常详细的微结构特征，如纤维卷曲，到更大尺度的管子大小和形状。该项目将是朝着根据青光眼的解剖学诊断青光眼风险的最终目标迈出的重要一步，并将为制定战略和干预措施提供一个强大的平台，以降低风险，保护视力，改善健康。

DESCRIPTION (provided by applicant): Detection and treatment of early glaucoma would be greatly enhanced by the development of a technique to evaluate the risks of glaucoma of an eye based on its architecture, and a more thorough understanding of the mechanisms leading to neural tissue degeneration. Our goal is to identify properties of the eye that predict susceptibiliy to neural tissue damage before it occurs. Early glaucomatous neural tissue degeneration is often localized to specific regions of the optic nerve head (ONH), and aging and elevated intraocular pressure (IOP) increase the risk for developing glaucoma. Our central hypothesis is that the architecture of the connective tissues of the ONH, and in particular of the lamina cribrosa within, determines the local robustness and sensitivity to IOP, and with this the regional susceptibility to neural tissue damage in early glaucoma. We have developed novel imaging techniques to obtain previously inaccessible micron-scale information of the tissues of the ONH, including detailed maps of collagen fiber alignment and the degree of stretch or relaxation of the fibers, referred to as crimp. With this information we characterize in high detail the architecture of the human lamina cribrosa and surrounding tissues at normal and elevated IOP. In Aim 1 we test the prediction that there is an association between regional susceptibility to neural tissue damage in early glaucoma and tissue architecture. In Aim 2 we test the prediction that the regions of known susceptibility to early glaucomatous damage are more sensitive to elevated IOP, in that the collagen fibers in the lamina trabeculae of these regions are the first to stretch and lose all crimp when reaching elevated IOP. We also test the hypotheses that aging is associated with changes in the tissue architecture such that older eyes are less robust than younger eyes. In Aim 3 we use numerical modeling to determine the functional relationship between age and tissue architecture and sensitivity to IOP, and test the hypotheses that the architectures of the lamina cribrosa and peripapillary sclera are major determinants of the local sensitivity to IOP, and that age- related changes in tissue architecture increase the sensitivity t IOP. This project will result in the most detailed characterization yet of the architecture of the tissues of the ONH, and of their changes with age. We will develop a comprehensive model for understanding the key elements of architecture that determine the local sensitivity to IOP, and identify characteristics of ONH architecture that are associated with the regional susceptibility t neural tissue damage in early glaucoma. This characterization will span multiple scales, from highly detailed micro-architectural features of the collagen fibers, such as fiber crimp, to the larger scale canal size and shape. This project will be an important step towards the ultimate goal of diagnosing eyes at risk of glaucoma based on their anatomy, and will provide a powerful platform for developing strategies and interventions to mitigate the risk and preserve vision, improving health.