Ocular Diurnal Rhythms and Eye Growth

眼部昼夜节律和眼睛生长

• 批准号: 8045389
• 负责人: DEBORA L NICKLA
• 金额: $ 24.96万
• 依托单位: NEW ENGLAND COLLEGE OF OPTOMETRY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8045389
• 关键词: Acetylcholine; Affect; Ametropias; Apomorphine; Asia; Atropine; Birds; Blinded; Blindness; Brain; Cholinergic Antagonists; Choroid; Chronotherapy; Circadian Rhythms; Degenerative Myopia; Dependence; Developed Countries; Dopamine; Dopamine Agonists; Environment; Epidemic; Eye; Eyeglasses; Financial compensation; Grant; Growth; Growth Factor; Health; Hyperopia; Image; In Vitro; Laboratories; Lead; Length; Lesion; Link; Malignant Neoplasms; Mammals; Mediating; Mediator of activation protein; Myopia; Neurons; Nitric Oxide; Optic Nerve; Pathology; Pathway interactions; Pharmacotherapy; Phase; Physiological; Play; Population; Porifera; Production; Regulation; Relative (related person); Retina; Retinal; Role; Sclera; Signal Transduction; Signaling Molecule; Thick; Time; United States; Vascular Smooth Muscle; Vision; Visual; Work; emmetropization; information gathering; lens; nerve supply; postnatal; prevent; response; therapy development

DESCRIPTION (provided by applicant): In the United States, myopia affects nearly 25% of the population, while in certain other developed countries the proportion of the population affected increases to 80% or more. Pathological myopia is also a leading cause of blindness. Therefore, understanding the mechanisms underlying the regulation of ocular growth is critical towards understanding how and why it goes awry in eyes that develop ametropias. Much of my work has examined the influence of ocular circadian rhythms in eye growth regulation. Understanding these influences might lead to the development of therapies that are time-dependent (chronotherapies), as has been found for other pathologies, including cancer. During the previous grant period, I have established that there is a tight link between increases in choroidal thickness and inhibition of ocular elongation. Furthermore, we found that the gaseous transmitter nitric oxide (NO) might influence the changes in choroidal thickness that in turn may influence ocular growth. NO is produced by the choroid, and inhibiting its synthesis pharmacologically prevents both the choroidal and growth responses to defocus. Choroidal NO also shows a circadian rhythm in vitro. I now propose to examine the specific role of the choroid in the visual regulation of eye growth. I propose to study three signal molecules--nitric oxide (NO), dopamine, and acetylcholine (ACh)-in relation to choroidal thickening and ocular growth. Do both dopamine and ACh influence NO and/or choroidal thickness? Is NO the mediator of the choroidal response or independent of it? And, where in the signal cascade do these molecules exert their effect? Finally, I have previously found that the phase difference between the circadian rhythm of ocular elongation and that of choroidal thickness is correlated with both the changes in choroidal thickness and ocular length. I now ask whether this phase difference is essential for lens-compensation, and, by implication, for emmetropization in general. The results from these Aims will bring us closer to understanding the signal cascade mediating changes in ocular growth. Aim 1: To determine the role of the parasympathetic and sympathetic innervation to the choroid in the choroidal and growth response. Aim 2. To determine the roles of dopamine and acetylcholine in the choroidal and growth responses and how they may influence NO production. Aim 3. To distinguish between the phase advance in the choroidal thickness rhythm and a phase-dependence of the transient choroidal responses in emmetropization. PUBLIC HEALTH RELEVANCE: Myopia is reaching epidemic proportions in Asia and pathological myopia is a leading cause of blindness. Understanding how the environment (vision) influences the signal cascade between retina and sclera to produce myopia is crucial to developing drug therapies that will ameliorate it. By the same token, understanding the roles of ocular physiological rhythms in eye growth control is crucial to determining whether these therapies might depend on time of day (chronotherapy), as has been found in other pathologies, including certain cancers.

描述（由申请人提供）：在美国，近视影响近25%的人口，而在某些其他发达国家，受影响的人口比例增加到80%或更多。病理性近视也是导致失明的主要原因。因此，了解眼睛生长调节的机制对于理解发展屈光不正的眼睛如何以及为什么会出错至关重要。我的大部分工作都是研究眼睛昼夜节律对眼睛生长调节的影响。了解这些影响可能会导致时间依赖性疗法（时间疗法）的发展，就像在其他病理学中发现的那样，包括癌症。在上一个资助期间，我已经确定了脉络膜厚度的增加和眼球伸长的抑制之间有密切的联系。此外，我们发现气态递质一氧化氮（NO）可能会影响脉络膜厚度的变化，从而影响眼部生长。NO由脉络膜产生，抑制其合成可防止脉络膜和生长对散焦的反应。脉络膜NO在体外也表现出昼夜节律。我现在打算研究脉络膜在眼睛生长的视觉调节中的特殊作用。我建议研究三个信号分子-一氧化氮（NO），多巴胺和乙酰胆碱（ACh）-与脉络膜增厚和眼生长。多巴胺和乙酰胆碱是否影响NO和/或脉络膜厚度？NO是脉络膜反应的介质还是独立于脉络膜反应？那么，这些分子在信号级联的哪个环节发挥作用呢？最后，我以前发现，眼伸长的昼夜节律和脉络膜厚度的昼夜节律之间的相位差与脉络膜厚度和眼长度的变化相关。我现在要问的是，这种相位差对于透镜补偿是否是必要的，并且，通过暗示，对于通常的正视化是否是必要的。这些目标的结果将使我们更接近于理解介导眼生长变化的信号级联。目的1：探讨脉络膜副交感神经和交感神经在脉络膜生长反应中的作用。目标二。确定多巴胺和乙酰胆碱在脉络膜和生长反应中的作用，以及它们如何影响NO的产生。目标3。区分正视化中脉络膜厚度节律的相位提前和瞬时脉络膜反应的相位依赖性。公共卫生相关性：近视在亚洲已达到流行病的比例，病理性近视是致盲的主要原因。了解环境（视觉）如何影响视网膜和巩膜之间的信号级联，从而产生近视，对于开发改善近视的药物疗法至关重要。同样，了解眼睛生理节律在眼睛生长控制中的作用，对于确定这些疗法是否可能依赖于一天中的时间（时间疗法）至关重要，就像在其他病理学中发现的那样，包括某些癌症。