Factors influencing the biomechanics of the lens

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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.