Biomechanics of the Aging Crystalline Lens

晶状体老化的生物力学

• 批准号: 1537027
• 负责人: giuliano scarcelli
• 金额: $ 32.76万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1537027&HistoricalAwards=false
• 关键词: Biomechanics; Aging; Crystalline; Lens

With aging, every person experiences presbyopia, an eye condition leading to the inability to see far and near objects in sharp focus. Current treatment options for presbyopia, either surgical or with spectacles, only improve vision at a fixed distance but do not restore the ability to actively change the focus distance, which is called ?accommodation.? Visual accommodation is governed by the deformability of the crystalline lens of the eye, which determines the ability to vary lens shape and thus focusing distance. Therefore, the fundamental understanding of the biomechanics of the crystalline lens and its aging process could lead to novel treatments for presbyopia. However, measuring the mechanical properties of the intact lens is difficult because mechanical testing methods are generally based on physical contact. The research addresses this need with a novel imaging modality, Brillouin microscopy, which can map lens properties without contact at high 3D resolution. The overall goal of this research program is to measure the biomechanics aging crystalline lens tissue using Brillouin technology in order to develop biomechanically-efficient approaches to delay presbyopia onset, slow progression and perhaps to restore accommodation. This project will advance the fundamental understanding of the accommodation process, thus addressing long-standing open questions in the field and providing potential solutions to presbyopia. Novel Brillouin microscopy will provide three-dimensional maps of the elastic modulus inside the lens and of its age-related changes. Development of a computational model of lens biomechanics and validation against gold-standard mechanical tests will enable testing the hypothesis that the spatial distribution of elastic modulus within the lens should be targeted to delay presbyopia onset or restore dynamic accommodation. Brillouin measurements and the validated model will be used to design and test three potential avenues to presbyopia-correction, i.e. limiting lens growth, disrupting protein crosslinking, and light-based localized micro-cutting. These are potentially effective solutions in increasing lens deformability and are compatible with current technological capabilities. In broader terms, the comprehensive information provided by Brillouin imaging could yield mechanistic insights into how accommodation is related to the underlying molecular processes, such as protein expression and micro-structural changes, which are responsible for the mechanical properties of the lens.

随着年龄的增长，每个人都会经历老花眼，这是一种导致无法清晰聚焦的远近物体的眼睛状况。目前老花眼的治疗方法，无论是手术还是配戴眼镜，只能在固定的距离上改善视力，但不能恢复主动改变焦距的能力，这被称为调节。视觉调节是由眼睛晶状体的变形能力决定的，这决定了改变晶状体形状和聚焦距离的能力。因此，对晶状体的生物力学及其老化过程的基本了解可能会导致治疗老花眼的新方法。然而，测量完整镜片的机械性能是困难的，因为机械测试方法通常是基于物理接触的。这项研究通过一种新的成像方式-布里渊显微镜满足了这一需求，它可以在高3D分辨率下非接触地绘制透镜的属性。这项研究计划的总体目标是利用布里渊技术测量老化晶体晶体组织的生物力学性能，以开发生物力学有效的方法来延缓老花眼的发病、缓慢进展，并可能恢复调节。该项目将促进对调节过程的基本了解，从而解决该领域长期存在的悬而未决的问题，并提供潜在的解决老花眼的方案。新型布里渊显微镜将提供晶状体内部弹性模数及其随年龄变化的三维地图。开发晶状体生物力学的计算模型，并根据黄金标准的机械测试进行验证，将能够检验晶状体内弹性模数的空间分布应针对延缓老花眼发病或恢复动态调节的假设。布里渊测量和验证的模型将用于设计和测试三种矫正老花眼的潜在途径，即限制晶状体生长、干扰蛋白质交联和基于光的局部显微切割。这些都是提高透镜变形性的潜在有效解决方案，并与当前的技术能力兼容。更广泛地说，布里渊成像提供的全面信息可以产生关于调节如何与潜在的分子过程相关的机械性见解，例如蛋白质表达和微结构变化，这是导致晶状体机械特性的原因。