Extra-lenticular aspects of accommodation and presbyopia

描述（由申请人提供）：我们对老花眼的病理生理学研究，即与年龄有关的眼睛聚焦近距离物体能力的丧失，已经在猴子模型中发现证据，老化的睫状肌受到其后部弹性附着物的限制，无法进行适应性运动。在家长R21资助申请中，我们的目标是确定后视带在调节和老花眼中的作用。在本补充申请（通知号：no - od -09-058）中，我们希望通过确定脉络膜（睫状肌的另一种后部弹性附着物）在限制睫状肌随年龄调节运动中的作用来扩大我们的研究。人类的调节振幅（眼睛聚焦近距离物体的能力）随着年龄的增长而逐渐下降，从生命的第二个十年甚至更早开始，到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，并且可以通过各种光学手段加以纠正，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。虽然亚灵长类动物的眼睛要么不适应，要么适应的机制与人类非常不同，但恒河猴眼睛的适应器官与人类的眼睛非常相似。恒河猴适应能力在相对时间尺度上的下降与人类基本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。[7,8]这限制了可调节振幅的程度。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。[7,8]此外，虽然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前/内向静止位置，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）。经典的教学将老花眼归因于“晶状体硬化”或“晶状体硬化”[2,9 -15]，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。

DESCRIPTION (provided by applicant): Our research into the pathophysiology of presbyopia, the age-related loss of the eye's ability to focus on near objects, has found evidence in a monkey model that the aging ciliary muscle is restricted in accommodative movement by its posterior elastic attachments. In the Parent R21 grant application, our goal is to determine the role of the posterior zonule in accommodation and presbyopia. In this supplement application (Notice number: NOT-OD-09-058) we wish to expand our investigation by determining the role of the choroid, another of the ciliary muscle's posterior elastic attachments, in restricting the accommodative movement of the ciliary muscle with age. Human accommodative amplitude (the ability of the eye to focus on near objects) declines progressively with age, beginning in the second decade of life and perhaps earlier, and is completely gone by age 50-55 years.[1] 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.[2] 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,[3] the accommodative apparatus of the rhesus monkey eye is very similar to that of the human eye.[4] [5] [6] Rhesus accommodation declines on a relative time scale that is essentially identical to that of the human.[5] 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.[7, 8] 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.[7, 8] 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,"[2, 9-15] 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). 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).