Extra-lenticular aspects of accommodation and presbyopia

描述（由申请人提供）：人的反射幅度（眼睛聚焦于附近物体的能力）逐渐下降，从生命的第二个十年开始，也许更早，并在50-55岁时完全消失。5没有人可以幸免，使老花眼（字面意思是“老眼”）成为世界上最常见的眼部疾病。虽然肯定不是致盲的条件，并通过各种光学手段纠正，老花眼的设备成本和生产力损失是巨大的。6虽然已经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，但回答一些最关键的问题所需的侵入性技术不能在活体中使用。虽然亚灵长类动物的眼睛要么不适应，要么适应机制与人类非常不同，7.恒河猴眼睛的反射器与人眼非常相似。10恒河猴的适应性下降的相对时间尺度基本上与人类相同。10我们的研究小组利用恒河猴提供了与以下相关的重要新信息：老视病理生理学在该模型中，我们已经证明，调节过程中的睫状体偏移随着年龄的增长而减少，这可能是由于年龄相关的后附件弹性降低。11，12这限制了调节幅度的程度。我们还表明，透镜赤道的运动随着年龄的增长而减少，再次导致降低的屈光振幅。11，12此外，尽管从切除的死后人眼的组织学数据显示，老年人睫状体处于前/向内位置，但我们的初步成像数据表明，在体内可能不是这种情况（见初步研究）。经典的教导将老花眼归因于“晶状体硬化”或“透镜硬化“，6，13-19，使得透镜不能改变形状，但是导致老花眼的确定机制仍然是难以捉摸的。在寻找一种方法来恢复一定程度的振幅，我们假设，年龄相关的肌肉不动是由于后方的限制。此外，如果这些后部限制被消除，肌肉的活动性可以恢复，并有助于调节人工晶状体（IOL）的功能。我们的目标有两个方面：1）研究和确定晶状体外器组件在年龄相关性睫状肌不动中的作用，这可能对保持睫状体（FCB）向前运动和实现下一代调节性IOL的功能至关重要; 2）确定猴子对人类情况的预测相关性。我们寻求对灵长类动物老花眼的机制有更全面的了解，并确定人类治疗的生物靶点，但不一定要确定针对人眼中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中年龄相关性睫状肌不动的病理生理学中起什么作用，并确定所得模型是否与人类老花眼相关。这对于实现下一代人工晶状体（IOL）的功能至关重要。

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).