Optic nerve head microstructure, biomechanics and susceptibility to glaucoma

项目摘要/摘要 早期青光眼的检测和治疗将通过开发一种技术来大大提高 根据青光眼的结构评估青光眼的风险，并更彻底地了解 导致神经组织退化的机制。我们的目标是识别眼睛的特性来预测 在神经组织损伤发生之前就对其易感性。早期青光眼神经组织变性是 通常局限于视神经头(ONH)的特定区域，以及衰老和眼压升高 (眼压)增加患青光眼的风险。我们的中心假设是 ONH的结缔组织，特别是内部的筛板，决定了局部的健壮性 以及对眼压的敏感性，以及与此相关的对早期青光眼神经组织损伤的区域易感性。 我们已经开发了新的成像技术来获得以前无法获取的微米级的信息 ONH的组织，包括胶原纤维排列和拉伸程度的详细地图 纤维松弛，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 预测在早期神经组织损伤的区域易感性之间存在关联 青光眼和组织结构。在目标2中，我们测试了已知的易感区域对 早期青光眼的损害对高眼压更敏感，因为板层中的胶原纤维 当眼压升高时，这些区域的小梁最先伸展并失去所有卷曲。我们还测试了 认为衰老与组织结构变化有关的假说，即年龄较大的眼睛较少 比年轻的眼睛更强壮。在目标3中，我们使用数值模拟来确定函数关系 年龄、组织结构和对眼压的敏感度之间的关系，并测试 筛板和乳头周围巩膜是局部对眼压敏感的主要决定因素，而年龄- 组织结构的相关变化增加了对眼压的敏感性。 该项目将产生迄今为止对ONH组织结构的最详细的描述， 以及它们随年龄的变化。我们将开发一个全面的模型，以了解 架构，确定本地对IOP的敏感度，并确定ONH架构的特征 与早期青光眼对神经组织损伤的区域易感性有关。这一特征将 跨越多个尺度，由高度精细的微结构特征的胶原纤维，如纤维 卷曲，以更大的规模渠道的大小和形状。这个项目将是迈向最终目标的重要一步。 根据青光眼的解剖学诊断青光眼的风险，并将为 制定战略和干预措施，以降低风险，保护视力，改善健康。

Project Summary / Abstract 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 susceptibility 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 to 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 to 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.