Biomechanics of the Aging Crystalline Lens

随着年龄的增长，每个人都会经历老花眼，这是一种眼睛疾病，导致无法在清晰的焦点下看到远近的物体。目前老花眼的治疗选择，无论是手术还是配戴眼镜，都只能改善固定距离的视力，而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可变形性决定的，它决定了改变晶状体形状和聚焦距离的能力。因此，对晶状体生物力学及其老化过程的基本理解可能会导致老花眼的新治疗方法。然而，由于机械测试方法通常基于物理接触，因此测量完整透镜的机械性能是困难的。该研究通过一种新的成像方式——布里渊显微镜来解决这一需求，布里渊显微镜可以在没有接触的情况下以高3D分辨率绘制透镜特性。本研究项目的总体目标是利用布里渊技术测量生物力学老化的晶状体组织，以开发生物力学有效的方法来延缓老花眼的发生、减缓进展，并可能恢复适应性。该项目将促进对住宿过程的基本理解，从而解决该领域长期存在的开放性问题，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的弹性模量及其与年龄相关的变化的三维地图。晶状体生物力学计算模型的开发和金标准力学试验的验证将能够验证晶状体内弹性模量的空间分布应该有针对性地延迟老花眼的发生或恢复动态调节的假设。布里渊测量和验证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。这些都是提高透镜变形能力的潜在有效解决方案，并且与当前的技术能力相兼容。从更广泛的角度来看，布里渊成像提供的综合信息可以产生机制见解，了解调节如何与潜在的分子过程相关，例如蛋白质表达和微观结构变化，这些过程负责透镜的机械性能。

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.