EXTRA-LENTICULAR ASPECTS OF ACCOMMODATION AND PRESBYOPIA

调节和老花眼的晶状体外方面

• 批准号: 8173152
• 负责人: PAUL L KAUFMAN
• 金额: $ 3.1万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173152
• 关键词: Age; Aging; Anterior; Applications Grants; Autopsy; Choroid; Ciliary Body; Ciliary Muscle; Computer Retrieval of Information on Scientific Projects Database; Data; Devices; Educational process of instructing; Elasticity; Eye; Functional disorder; Funding; Goals; Grant; Human; Image; Individual; Institution; Intraocular lens implant device; Investigation; Life; Macaca mulatta; Modeling; Monkeys; Movement; Muscle; Optics; Parents; Play; Positioning Attribute; Presbyopia; Productivity; Relative (related person); Research; Research Personnel; Resources; Rest; Role; Sclerosis; Shapes; Source; Techniques; Time; Tissues; United States National Institutes of Health; age related; cost; in vivo; lens; next generation; nonhuman primate; public health relevance

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To determine what role the extralenticular tissues play in the pathophysiology of age-related ciliary muscle immobility. 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).

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：探讨晶状体外组织在老年性睫状肌不动的病理生理机制中的作用。 我们对老花眼的病理生理学的研究发现，在猴子模型中，老化的睫状肌在调节运动中受到其后部弹性附着物的限制。老花眼是一种与年龄相关的眼睛对近距离物体的关注能力的丧失。在父母的R21赠款申请中，我们的目标是确定后小带在调节和老花眼中的作用。在本补充申请(通知编号：NOT-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的调节运动中的作用来扩大我们的研究范围。人类的调节幅度(眼睛聚焦于近处物体的能力)随着年龄的增长而逐渐下降，从人生的第二个十年开始，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纠正，但老花眼在设备上的成本和生产力的损失是巨大的。[2]尽管从活体和死后的人眼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，[3]恒河猴眼睛的调节器官与人眼非常相似。[4][5][6]恒河猴调节能力下降的相对时间尺度基本上与人类相同。[5]我们的研究小组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。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。[7，8]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前/内位置，但我们有初步的成像数据表明，活体情况可能并非如此(参见初步研究)。经典教学将老花眼归因于“晶状体硬化”或“晶状体硬化”[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。 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。