Factors influencing the biomechanics of the lens

随着年龄的增长，人们对近距离物体的注意力会下降。这种视力下降被称为老花眼，几乎影响到所有40岁以上的人。据估计，全球劳动力中未矫正的老花眼造成的生产力损失高达110亿美元。老花眼的原因尚不清楚，但大多数研究指出是内部生物晶状体变硬。通常，在年轻的眼睛中，这种结构是动态的，它与睫状肌和睫状肌带一起作用，以增加光功率。这个过程被称为调节，包括睫状肌的收缩，导致晶状体膨胀，以及清晰聚焦近距离物体的能力。在鸟类中也观察到老花眼，这表明所有动物通过改变晶状体形状来聚焦的共同机制。这项研究计划的长期目标是了解晶状体等运动部件如何保持动态行为，以及它们的运动如何影响眼睛的其他部分。为了实现这一总体目标，了解镜头是如何适应的是必要的。短期的研究目标将是确定1)晶状体中的两种蛋白质，肌动蛋白和肌球蛋白是否影响晶状体的生物力学；2)晶状体内是否需要水流来改变晶状体的形状。由于有一些迹象表明晶状体运动可能会对视网膜造成长期压力，视网膜是眼睛后部负责捕捉图像的组织，因此提出了另一项研究：开发一种测试，直接测量调节对视网膜功能的影响。对于O1，我和我的学生将专注于结构蛋白actin。肌动蛋白还与分子马达肌球蛋白相互作用，在许多细胞中产生运动或收缩张力。由于晶状体是动态的，这些分子马达是增加还是减少了晶状体形状的变化，这个问题需要回答。肌动蛋白和肌球蛋白在晶状体中的分布将被映射到三维空间，形成一个模型。我们将模拟肌动蛋白和肌凝蛋白在模型中的相互作用，以确定适应性是否以及如何受到影响。对于O2，我们将测试当透水性增加或减少时是否以及如何影响调节。我们将以水通道蛋白为目标，因为水的渗透性是由这些蛋白质调节的。我们的最终目标（O3）将涉及开发一种新的方法来测量视网膜功能的鸡眼，诱导适应。我实验室的学生将受益于学习新的研究和技术技能，这将为他们未来在学术界或工业界的职业生涯提供工具。他们的工作将揭示晶状体如何改变形状的新信息，以及我们是否可以在未来利用这些知识来保持老化的眼睛的适应性。

With age, the ability to focus on near objects declines. This decline, called presbyopia, affects almost everyone over the age of 40, and the loss of productivity from uncorrected presbyopia in the work force is estimated to be $11 billion globally. The reasons for presbyopia are unclear, but most studies point to stiffening of the internal biological, crystalline lens. Normally, in young eyes, this structure is dynamic and acts together with the ciliary muscle and zonules to increase optical power. This process, called accommodation, involves contraction of the ciliary muscle, leading to bulging of the lens and the ability to focus on near objects clearly. Presbyopia is also observed in birds, suggesting a common mechanism for all animals that focus by changing the shape of the lens. The long-term goal of the proposed research program is to understand how moving components, such as the lens, maintain dynamic behaviour, and how their movements affect other parts of the eye. To achieve this overarching goal, an understanding of how the lens accommodates is necessary. The short-term research objectives will be to determine O1) whether two proteins in the lens, actin and myosin affect the biomechanics of lenses and O2) whether water flow within the lens is required for lenses to change shape. As there are some indications that lens movements might cause long-term stress on the retina, the tissue at the back of the eye responsible for capturing images, one other study is proposed: O3) to develop a test that directly measures the effects of accommodation on retinal function. For O1, my students and I will focus on the structural protein actin. Actin also interacts with the molecular motor, myosin, to generate movement or contractile tone in many cells. Since the lens is dynamic, the question of whether these molecular motors add or detract from lenticular shape-changes needs to be answered. Actin and myosin distributions in the lens will be mapped in three-dimensional space to form a model. We will simulate actin and myosin interacting in the model to determine if and how accommodation is affected. For O2, we will test if and how accommodation is affected when the water permeability is increased or decreased. We will target aquaporins, since water permeability is regulated by these proteins. Our final objective (O3) will involve developing a novel method for measuring retinal function from chicken eyes that are induced to accommodate. Students in my lab will benefit from learning new research and technical skills, which will provide them with tools for their future careers in academia or industry. Their work will uncover new information about how the lens changes shape, and whether we can harness this knowledge in the future to maintain accommodation in the ageing eye.