Ocular Diurnal Rhythms and Eye Growth

眼部昼夜节律和眼睛生长

基本信息

批准号：
8238361
负责人：
DEBORA L NICKLA
金额：
$ 25.2万
依托单位：
NEW ENGLAND COLLEGE OF OPTOMETRY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-08-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8238361
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

项目摘要

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，人口的比例增加到80％或更多。病理近视也是失明的主要原因。因此，了解调节眼生长的机制对于理解它如何以及为什么在发展呈抗肌瘤的眼睛中出现问题至关重要。我的大部分工作都研究了眼部昼夜节律对眼睛生长调节的影响。理解这些影响可能会导致时间依赖性的疗法的发展（年代疗法），如其他病理（包括癌症）所发现的那样。在上一个赠款期间，我确定脉络膜厚度的增加与抑制眼伸长之间存在紧密联系。此外，我们发现气态发射器一氧化氮（NO）可能会影响脉络膜厚度的变化，而脉络膜厚度可能会影响眼部生长。 NO是由脉络膜产生的，并在药理上抑制其合成，可防止脉络膜和生长对散焦的反应。脉络膜NO还显示了体外的昼夜节律。我现在建议检查脉络膜在视觉调节眼睛生长中的特定作用。我建议研究三个信号分子 - 一种氧化物（NO），多巴胺和乙酰胆碱（ACH） - 与脉络膜增厚和眼部生长有关。多巴胺和ACH都会影响NO和/或脉络膜厚度吗？没有脉络膜反应的中介或独立于此的中介者？而且，在信号级联中，这些分子在哪里发挥作用？最后，我以前已经发现，眼部伸长的昼夜节律与脉络膜厚度的昼夜节律之间的相差与脉络膜厚度和眼长长度的变化相关。现在，我问这个相位差异对于镜头补偿是否至关重要，并且对整个透气化是否至关重要。这些目标的结果将使我们更加了解眼部增长的信号级联介导的变化。目的1：确定对脉络膜和脉络膜生长反应中副交感神经和交感神经的作用。目的2。确定多巴胺和乙酰胆碱在脉络膜和生长反应中的作用，以及它们如何影响没有生产。 AIM 3。区分脉络膜厚度节奏中的相位和瞬时脉络膜响应在弹性化中的相位依赖性。公共卫生相关性：近视在亚洲达到流行比例，病理近视是失明的主要原因。了解环境（视觉）如何影响视网膜和巩膜之间产生近视的信号级联反应对于开发会改善其改善的药物疗法至关重要。同样，了解眼生理节奏在眼睛生长控制中的作用对于确定这些疗法是否可能取决于一天中的时间（年代疗法），这是在其他病理学（包括某些癌症）中发现的。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nitric oxide synthase inhibitors prevent the growth-inhibiting effects of quinpirole.

DOI：
10.1097/opx.0000000000000041
发表时间：
2013-11
期刊：
Optometry and vision science : official publication of the American Academy of Optometry
影响因子：
0
作者：
Nickla DL;Lee L;Totonelly K
通讯作者：
Totonelly K

Inhibiting the neuronal isoform of nitric oxide synthase has similar effects on the compensatory choroidal and axial responses to myopic defocus in chicks as does the non-specific inhibitor L-NAME.