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进行的研究，即与年龄相关的眼睛聚焦近距离物体能力的丧失，在猴模型中发现了证据，表明老化的睫状肌通过其后部弹性附件限制了反射运动。在父母R21资助申请中，我们的目标是确定后悬韧带在调节和老花眼中的作用。在本补充申请（通知号：NOT-OD-09-058）中，我们希望通过确定脉络膜（睫状肌的另一个后部弹性附件）在限制睫状肌随年龄的收缩运动中的作用来扩展我们的研究。 人类的视幅度（眼睛聚焦于附近物体的能力）随着年龄的增长而逐渐下降，从生命的第二个十年开始，也许更早，到50-55岁时完全消失。[1]没有人能幸免，这使得老花眼（字面意思是“老眼”）成为世界上最常见的眼部疾病。虽然肯定不是致盲状态，并且可以通过各种光学手段矫正，但老花眼的设备成本和生产力损失是巨大的。[2]虽然许多有用的和相关的信息已经从活体和死后人眼的研究中获得，但回答一些最关键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，[3]恒河猴眼睛的反射器官与人类眼睛非常相似。[4][5] [6]恒河猴的适应能力下降的相对时间尺度基本上与人类相同。[5]我们的小组已经利用恒河猴来提供与老视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，睫状体漂移调节过程中随着年龄的增长而减少，可能是由于年龄相关的后附件的弹性下降。[7，8]这限制了振幅的振幅。我们还表明，透镜赤道的运动随着年龄的增长而减少，再次导致反射振幅的减少。[7，8]此外，虽然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，但我们有初步的成像数据表明，体内情况可能并非如此（见初步研究）。经典的教学将老视归因于“晶状体硬化”或“透镜硬化"[2，9-15]，使得透镜不能改变形状，但是导致老视的确切机制仍然难以捉摸。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。 公共卫生相关性：我们的目标是确定晶状体外组织在非人灵长类动物中年龄相关的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): 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).