Vision, eye growth rhythms and retinal signals in refractive development

屈光发育中的视力、眼睛生长节律和视网膜信号

• 批准号: 10438823
• 负责人: DEBORA L NICKLA
• 金额: $ 65.99万
• 依托单位: NEW ENGLAND COLLEGE OF OPTOMETRY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10438823
• 关键词: 3,4-Dihydroxyphenylacetic Acid; Address; Adult; Affect; Animal Model; Animals; Area; Atropine; Beds; Blindness; Cataract; Cells; Chick; Child; Childhood; Choroid; Circadian Rhythms; Clinical; Clock protein; Cone; Contact Lenses; Cornea; Development; Disease; Dopamine; Drops; Environment; Etiology; Exposure to; Eye; Genes; Glaucoma; Growth; Health; Hour; Human; Incidence; Knowledge; Laboratory Research; Light; Lighting; Link; Measures; Mediating; Melatonin; Messenger RNA; Molecular; Myopia; Optic Nerve; Optics; Persons; Photosensitivity; Play; Prevalence; Prophylactic treatment; Public Health; Refractive Errors; Research; Retina; Retinal Diseases; Retinal Ganglion Cells; Role; Sampling; Sclera; Series; Signal Pathway; Signal Transduction; Sleep; System; Technology; Thick; Time; Time Study; Tissues; Transcript; Vision; Visual; Visual impairment; Work; circadian; circadian pacemaker; deprivation; emmetropization; experimental study; interdisciplinary collaboration; interest; lens; luminance; melanopsin; neurosensory; novel; response; retinal imaging; side effect; transcriptome sequencing

Project Summary The reasons behind the development of myopia and its increasing incidence, particularly among educated people, remain obscure. The finding that animals can be made myopic or hyperopic by spectacle lenses that shift the plane of focus to behind the retina (hyperopic defocus) or in front of it (myopic defocus) demonstrates that refractive development is under homeostatic control. Because the eye can modulate its growth even if the optic nerve is severed, and because defocus that is restricted to one area only affects the eye growth underlying that area, it follows that the retina controls eye growth. However, despite two centuries of study, prophylactic treatments against childhood myopia are limited to atropine drops, contact lenses that reshape the cornea, or stabilizing treatments for the sclera, all of which have potential side effects and limited efficacy. Decades of work in our three labs has linked the development of ametropias to alterations in ocular circadian rhythms. Recently, we showed that the eye’s response to defocus depended on time of day of exposure, further evidence for the influence of circadian rhythms in myopia development. We also found that 6 clock genes in retina and choroid were altered in eyes responding to myopic or hyperopic defocus. In this application we will look for downstream signals of these clock genes using RNA-Seq to determine molecular signaling pathways that might explain what to target in potential myopia therapies. How the visual environment affects the growth of the eye and influences refractive error in humans continues to generate interest, including contemporary studies relating time spent outdoors to the inhibition of myopia in children, and on the deleterious impact of artificial nighttime lighting on human health in general. Increasing evidence indicates that exposure to light in the evening, especially short wavelengths, affects sleep cycles by altering the rhythm in melatonin. We found that a mere 2 hours of blue evening light stimulated ocular growth and altered ocular rhythms. This application will address the influences of time of day, relative spectral composition and the dopamine and melatonin rhythm on the responses to brief blue light. We will study the role of the ipRGCs, and the potential interaction between hyperopic defocus and blue light. These studies will have implications for the use of light-emitting technologies prior to bed. Our finding that six clock gene transcripts, and melanopsin, showed diurnal cycling in choroid suggests diverse circadian functions for this tissue. We aim to study circadian signaling in choroid, with focus on roles of dopamine and melanopsin. We will localize melanopsin, and in an exploratory series of experiments, we will ask if the rhythm in choroidal thickness is endogenous to the choroid, and address the hypothesis that the choroid is photosensitive. We will use chicks, a species with rapid and well-characterized compensatory responses to visual manipulations, and retinal/visual similarities to humans. We expect that this work will generate novel and useful hypotheses that can be extended to the study of refractive errors in children.

项目概要 近视发展及其发病率增加的原因，特别是在受过教育的人群中 人，依然默默无闻。研究发现动物可以通过眼镜片而变得近视或远视 将焦点平面移动到视网膜后面（远视散焦）或前面（近视散焦） 屈光发育处于稳态控制之下。因为眼睛可以调节其生长，即使 视神经被切断，并且由于仅限于某一区域的散焦仅影响眼睛的生长 在该区域的下面，视网膜控制着眼睛的生长。然而，尽管经过两个世纪的研究， 儿童近视的预防性治疗仅限于阿托品滴剂、重塑视力的隐形眼镜 角膜或巩膜稳定治疗，所有这些都有潜在的副作用和有限的疗效。 我们三个实验室数十年的工作已将屈光不正的发展与眼部昼夜节律的改变联系起来 节奏。最近，我们发现眼睛对散焦的反应取决于一天中的曝光时间， 进一步证明昼夜节律对近视发展的影响。我们还发现 6 个时钟 眼睛中视网膜和脉络膜的基因因近视或远视散焦而发生改变。在这个应用程序中 我们将使用 RNA-Seq 寻找这些时钟基因的下游信号以确定分子信号传导 可能解释潜在近视治疗目标的途径。 视觉环境如何影响眼睛的生长并影响人类的屈光不正 继续引起人们的兴趣，包括当代研究将户外活动时间与抑制 儿童近视，以及夜间人工照明对人类健康的有害影响。 越来越多的证据表明，晚上暴露在光线下，尤其是短波长的光线下，会影响睡眠 通过改变褪黑激素的节律来实现循环。我们发现，仅仅 2 小时的蓝色夜光就能刺激 眼睛生长和眼节律改变。该应用程序将解决一天中的时间、相对时间的影响 光谱成分以及多巴胺和褪黑激素节律对短暂蓝光的反应。我们将 研究 ipRGC 的作用，以及远视散焦和蓝光之间的潜在相互作用。这些 研究将对睡前使用发光技术产生影响。 我们发现六个时钟基因转录本和黑视蛋白显示脉络膜的昼夜循环表明 该组织具有多种昼夜节律功能。我们的目标是研究脉络膜的昼夜节律信号传导，重点关注角色 多巴胺和黑视素。我们将定位黑视蛋白，并在一系列探索性实验中，我们将 询问脉络膜厚度的节律是否是脉络膜内源性的，并提出以下假设： 脉络膜具有光敏性。我们将使用雏鸡，这是一种具有快速且特征良好的补偿性的物种 对视觉操作的反应以及与人类的视网膜/视觉相似性。我们期望这项工作将 产生新颖且有用的假设，可以扩展到儿童屈光不正的研究。

项目成果

The effects of brief high intensity light on ocular growth in chicks developing myopia vary with time of day.

• DOI: 10.1016/j.exer.2020.108039
• 发表时间: 2020-06
• 期刊: EXPERIMENTAL EYE RESEARCH
• 影响因子: 3.4
• 作者: Sarfare, Shanta;Yang, Jane;Nickla, Debora L.
• 通讯作者: Nickla, Debora L.

Effects of autonomic denervations on the rhythms in axial length and choroidal thickness in chicks.

自主神经去神经对雏鸡眼轴长度和脉络膜厚度节律的影响。

• DOI: 10.1007/s00359-018-01310-4
• 发表时间: 2019
• 期刊: Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology
• 作者: Nickla,DeboraL;Schroedl,Falk
• 通讯作者: Schroedl,Falk