Extra-lenticular aspects of accommodation and presbyopia

描述(申请人提供)：人类调节幅度(眼睛聚焦于近物体的能力)从第二个十年开始逐渐下降，也许更早，到50-55岁时完全消失。5没有一个人可以幸免，这使得老花眼(字面意思是“老眼”)成为世界上最常见的眼病。虽然老花眼肯定不是一种失明的情况，而且可以通过各种光学手段矫正，但老花眼在设备上的成本和生产力的损失是相当可观的。6尽管从活体和死后人眼的研究中获得了许多有用和相关的信息，但回答一些最关键问题所需的侵入性技术不能用于活人。虽然次灵长类物种的眼睛不能适应或不能适应与人类有很大不同的机制，7恒河猴眼睛的调节器官与人眼非常相似。8-10恒河猴调节能力下降的相对时间尺度基本上与人类相同。10我们的团队利用恒河猴提供了与老花眼病理生理学相关的重要新信息。在这个模型中，我们已经证明了睫状体在调节过程中的漂移随着年龄的增长而减少，这可能是由于与年龄相关的后部附着物弹性的降低。11、12这限制了调节幅度的程度。我们还发现，晶状体赤道的运动随着年龄的增长而减少，再次导致调节幅度降低。11、12此外，尽管解剖后的人眼组织学数据显示老年人的睫状体处于向前/向内的位置，但我们有初步的成像数据表明，活体情况可能并非如此(见初步研究)。经典教学将老花眼归因于“晶状体硬化症”或“晶状体硬化”，因此晶状体不能改变形状，但导致老花眼的确切机制仍然难以捉摸。为了寻找一种方法来恢复一定程度的调节幅度，我们假设与年龄相关的肌肉不动是由于后部限制。此外，如果消除这些后部限制，肌肉的活动度可以恢复，并有助于调节人工晶状体(IOL)的功能。我们的目标有两个：1)研究和确定调节机构的豆外部分在年龄相关性睫状肌不动中的作用，这可能是维持睫状体前向运动和使下一代调节性人工晶状体功能得以发挥的关键；2)确定猴子对人类情况的预测性相关性。我们试图更全面地了解灵长类动物老花眼的发病机制，并确定用于人类治疗的生物靶点，但不一定要确定针对人眼该靶点的治疗性外科手术。公共卫生相关性我们的目标是确定晶状体外组织在非人类灵长类动物年龄相关性睫状肌静止的病理生理学中所起的作用，并确定由此产生的模型是否与人类老花眼有关。这可能是实现下一代人工晶状体(IOL)功能的关键。

DESCRIPTION (provided by applicant): Human accommodative amplitude (the ability of the eye to focus on near objects) declines progressively, beginning in the second decade of life and perhaps earlier, and is completely gone by age 50-55 years.5 No individual appears exempt, making presbyopia (literally, "old eye") the most common ocular affliction in the world. Although certainly not a blinding condition, and correctable by various optical means, presbyopia's cost in devices and lost productivity is substantial.6 Although much useful and relevant information has been garnered from studies in living and postmortem human eyes, the invasive techniques required to answer some of the most critical questions cannot be employed in the living human. While the eyes of subprimate species either do not accommodate or accommodate by mechanisms very different from that of the human,7 the accommodative apparatus of the rhesus monkey eye is very similar to that of the human eye.8-10 Rhesus accommodation declines on a relative time scale that is essentially identical to that of the human.10 Our group has utilized the rhesus monkey to contribute significant new information relevant to presbyopia pathophysiology. In this model, we have demonstrated that the ciliary body excursion during accommodation diminishes with age, probably due to an age-related decrease in elasticity of the posterior attachments.11, 12 This restricts the degree of accommodative amplitude. We have also shown that the movement of the lens equator decreases with age, again resulting in reduced accommodative amplitude.11, 12 Further, although histological data from excised postmortem human eyes shows the older human ciliary body at rest in an anterior/inward position, we have preliminary imaging data that suggest this may not be the case in vivo (see Preliminary Studies). Classical teaching attributes presbyopia to "lenticular sclerosis," or "lens hardening,"6, 13-19 so that the lens cannot change shape, but the definitive mechanism that results in presbyopia remains elusive. In search of a way to restore some degree of accommodative amplitude, we hypothesize that age-related immobility of the muscle is due to posterior restriction. Further, if these posterior restrictions are eliminated, mobility of the muscle can be restored and facilitate the function of accommodating intraocular lenses (IOLs). Our goal is two fold: 1) To investigate and define the role of extralenticular components of the accommodative apparatus in age-related ciliary muscle immobility, which may be crucial in preserving forward ciliary body (FCB) movement and in enabling the function of the next-generation accommodating IOLs; and 2) To determine the predictive relevance of the monkey for the human situation. We seek to develop a more complete understanding of the mechanism of presbyopia in primates and to identify a biological target for human therapy, but not necessarily to identify a therapeutic surgical procedure for that target in the human eye. PUBLIC HEALTH RELEVANCE Our goal is to determine what role the extralenticular tissues play in the pathophysiology of age-related ciliary muscle immobility in the non-human primate, and to determine whether the resulting model is relevant to human presbyopia. This may be crucial in enabling the function of next- generation intraocular lenses (IOLs).