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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要近视发展及其发病率的原因，尤其是在受过教育的原因人们，保持晦涩难懂。发现动物可以通过奇观镜头使动物成为近视或远视的发现将焦点平面转移到视网膜后面（远视散焦）或前面（近视散焦）这种折射的发展受到稳态控制。因为即使眼睛也可以调节其生长视神经很严重，因为仅限于一个区域的散焦只会影响眼睛的生长在该区域的基础上，视网膜控制眼睛的生长。但是，要求两个世纪的研究，针对儿童近视的预防治疗仅限于阿托品下降，隐形眼镜重塑角膜或对巩膜的稳定处理，所有这些都有潜在的副作用和有限的有效性。在我们的三个实验室的数十年工作已经将阿米特罗皮亚的发展与眼昼夜节律的变化联系起来节奏。最近，我们表明眼睛对散焦的反应取决于暴露时间，进一步的证据证明了昼夜节律在近视发展中的影响。我们还发现6个时钟视网膜和脉络膜中的基因在响应近视或远视散焦的眼睛中改变了。在此应用程序中我们将使用RNA-Seq来寻找这些时钟基因的下游信号来确定分子信号可能解释潜在近视疗法中要靶向的途径。视觉环境如何影响眼睛的生长并影响人类的折射率继续引起兴趣，包括当代研究将花费的时间在户外与抑制儿童的近视以及人造夜间照明对人类健康的有害影响。越来越多的证据表明，晚上暴露于光线（尤其是短波长）会影响睡眠通过改变褪黑激素中的节奏来循环。我们发现只有2个小时的蓝色晚光刺激了眼部生长和眼节律改变。该应用程序将解决一天中时间的影响，相对光谱成分以及对短暂蓝光的反应的多巴胺和褪黑激素节奏。我们将研究IPRGC的作用，以及远视散焦与蓝光之间的潜在相互作用。这些研究将对床前发光技术的使用有影响。我们发现六个时钟基因转录本和黑色素蛋白在脉络膜中显示的昼夜循环表明该组织的各种昼夜节律功能。我们旨在研究脉络膜中的昼夜节信号，重点是多巴胺和黑色素蛋白。我们将定位黑色素蛋白，在一系列探索性实验中，我们将询问脉络膜厚度中的节奏是否对脉络膜内源性，并解决以下假设。脉络膜具有光敏性。我们将使用小鸡，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响应以及对人类的视网膜/视觉相似性。我们希望这项工作将产生新的和有用的假设，可以扩展到儿童折射错误的研究。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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
影响因子：
0
作者：
Nickla,DeboraL;Schroedl,Falk
通讯作者：
Schroedl,Falk