Biomechanics of the Aging Crystalline Lens

随着年龄的增长，每个人都会出现老花眼，这是一种导致无法清晰地看清远处和近处物体的眼部疾病。目前老花眼的治疗选择，无论是手术还是戴框架眼镜，只能改善固定距离处的视力，但不能恢复主动改变焦距的能力，这称为“调节”。 视觉调节由眼睛晶状体的可变形性控制，这决定了改变晶状体形状并从而改变聚焦距离的能力。因此，对晶状体生物力学及其老化过程的基本了解可能会带来新的老花眼治疗方法。然而，测量完整镜片的机械性能很困难，因为机械测试方法通常基于物理接触。该研究通过一种新颖的成像方式——布里渊显微镜来满足这一需求，它可以在不接触的情况下以高 3D 分辨率绘制镜头特性。该研究计划的总体目标是使用布里渊技术测量老化晶状体组织的生物力学，以开发生物力学有效的方法来延迟老花眼的发生、减缓进展，甚至可能恢复调节。该项目将增进对调节过程的基本理解，从而解决该领域长期存在的悬而未决的问题，并为老花眼提供潜在的解决方案。新型布里渊显微镜将提供晶状体内部弹性模量及其与年龄相关的变化的三维图。晶状体生物力学计算模型的开发和金标准机械测试的验证将能够测试这样的假设：晶状体内弹性模量的空间分布应该以延迟老花眼发作或恢复动态调节为目标。布里渊测量和经过验证的模型将用于设计和测试三种潜在的老花眼矫正途径，即限制晶状体生长、破坏蛋白质交联和基于光的局部微切割。这些是增加晶状体变形能力的潜在有效解决方案，并且与当前的技术能力兼容。从更广泛的角度来看，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分子过程相关的机制见解，例如蛋白质表达和微观结构变化，这些分子过程决定晶状体的机械性能。

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.