Extra-lenticular aspects of accommodation and presbyopia

描述（由申请人提供）：人类调节幅度（眼睛聚焦近物体的能力）在生命的第二个十年或更早开始逐渐下降，并在50-55岁时完全消失没有人能幸免，这使得老花眼（字面意思是“老眼睛”）成为世界上最常见的眼部疾病。虽然老花眼肯定不是致盲的情况，而且可以通过各种光学手段加以矫正，但老花眼在设备上的成本和生产力的损失是巨大的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体。虽然亚种灵长类动物的眼睛要么不能调节，要么调节的机制与人类的非常不同，但恒河猴眼睛的调节器官与人类的眼睛非常相似。恒河猴的适应能力在相对的时间尺度上下降，基本上与人类相同本小组利用恒河猴为老花眼病理生理提供了重要的新信息。在这个模型中，我们已经证明了调节过程中的纤毛体偏移会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减少。这限制了调节幅度的程度。我们还表明，晶状体赤道的运动随着年龄的增长而减少，再次导致调节幅度的减少。11,12此外，尽管从死后切除的人眼的组织学数据显示，老年人的睫状体处于静止的前/内向位置，但我们的初步成像数据表明，体内情况可能并非如此（见初步研究）。经典教学将老花眼归因于“晶状体硬化”或“晶状体硬化”6,13 -19，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振幅，我们假设与年龄相关的肌肉不动是由于后部限制。此外，如果消除这些后侧限制，肌肉的活动性可以恢复，并促进调节人工晶状体（iol）的功能。我们的目标有两个方面：1)研究和定义调节装置的外侧成分在年龄相关性睫状肌不动中的作用，这可能对保持睫状体向前运动和实现下一代调节IOLs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学靶点，但不一定要确定针对人眼靶点的治疗性外科手术。我们的目标是确定眼外组织在非人灵长类动物中与年龄相关的睫状肌不动的病理生理中所起的作用，并确定由此产生的模型是否与人类老花眼相关。这对于下一代人工晶状体（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).