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: 10183258
• 负责人: DEBORA L NICKLA
• 金额: $ 65.86万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10183258
• 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; 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.

项目摘要 近视发展和发病率上升的原因，特别是在受过教育的人群中 人，仍然默默无闻。动物可以通过眼镜镜片变得近视或远视， 将焦平面移到视网膜后面（远视散焦）或视网膜前面（近视散焦）， 屈光发育是在自我平衡的控制下进行的因为眼睛可以调节它的生长， 视神经被切断，并且因为散焦仅限于一个区域， 在这个区域的下面，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眼液，隐形眼镜重塑了近视眼的形状。 角膜或巩膜的稳定治疗，所有这些都具有潜在的副作用和有限的功效。 我们三个实验室数十年的工作已经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， 进一步证明了近视发展中昼夜节律的影响。我们还发现6点钟方向 在对近视或远视散焦有反应的眼睛中，视网膜和脉络膜中的基因发生改变。本申请中 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的目标的途径。 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，包括当代研究有关的时间花在户外的抑制 儿童近视，以及人工夜间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，特别是短波长的光线，会影响睡眠 通过改变褪黑激素的节律来调节循环。我们发现，仅仅2小时的蓝色黄昏光刺激 眼生长和眼节律改变。此应用程序将解决一天中的时间，相对 光谱组成和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，黑视素，显示昼夜周期脉络膜表明， 不同的昼夜节律功能我们的目标是研究脉络膜中的昼夜信号，重点是角色， 多巴胺和黑视素我们将定位黑视素，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，并解决以下假设： 脉络膜是感光的我们将使用小鸡，一种具有快速和良好特征的补偿性的物种， 对视觉操作的反应，以及与人类的视网膜/视觉相似性。我们希望这项工作将 产生新的和有用的假设，可以扩展到儿童屈光不正的研究。