Control of refractive development with temporally modulated light

用时间调制光控制屈光发展

• 批准号: 9110651
• 负责人: TIMOTHY J GAWNE
• 金额: $ 22.05万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9110651
• 关键词: Adolescent; Adult; Affect; American; Animal Model; Animals; Birth; Cataract; Characteristics; Child; Computers; Cone; Contact Lenses; Cues; Darkness; Data; Development; Distant; Ensure; Environment; Epidemic; Exposure to; Eye; Eyedrops; Far East; Feedback; Frequencies; Glass; Glaucoma; Grant; Growth; Hour; Human; Hyperopia; Image; Intervention; Japan; Lead; Length; Light; Lighting; Macular degeneration; Mammals; Methods; Modeling; Monocular Blindness; Muscarinic Antagonists; Myopia; Neurons; Operative Surgical Procedures; Ophthalmic examination and evaluation; Optics; Photoreceptors; Phototherapy; Population; Prevalence; Primates; Process; Psychological reinforcement; Public Health; Recovery; Refractive Errors; Reporting; Retina; Retinal Perforations; Risk; Risk Factors; Sclera; Signal Transduction; Solid; Stimulus; Testing; Tupaiidae; United States; Video Games; Vision; Visual; Work; base; cost; deprivation; design; emmetropization; experience; improved; juvenile animal; lens; man; postnatal; practical application; prevent; public health relevance; research study; success; theories; tool

 DESCRIPTION (provided by applicant): During postnatal development when the eye is still growing, a mechanism commonly referred to as the emmetropization mechanism uses the eye's refractive error to regulate the growth of the scleral shell to match the axial length of the eye t the focal plane. When functioning properly, this mechanism ensures that images will be sharply focused on the retina. The problem, for over 40% of Americans and up to 96% of groups in East Asia, is that the eye becomes too long for its own optics and is thus myopic. In addition to the cost (over $14 billion annually in the United States) of eye exams, glasses, contact lenses, and refractive surgery, even low amounts of myopia raise the risk of developing blinding conditions. Thus, effective strategies to slow eye growth and reduce the prevalence of juvenile-onset myopia in children are needed. Various strategies (bifocal glasses and contact lenses, muscarinic antagonist eye drops, scleral reinforcement surgery) have been developed to control axial elongation and myopia with limited success. An important problem is that we do not have a solid understanding of the visual cue or cues that are used by the emmetropization mechanism to determine if the eye is too short (hyperopia) and should increase its growth rate to achieve emmetropia, or if the eye is becoming too long (myopia) and should slow the axial elongation rate to match the maturation of the optics. We have developed a new theory of how the retina does this based on the temporal characteristics of fluctuations of in-focus vs. out-of-focus images experienced by photoreceptors and the neurons to which they connect. This has led us to discover two stimuli that have powerful effects on refractive development in young tree shrews, a cone-dominated dichromatic mammal closely related to primates: (1) Ambient long wavelength (628 ± 10 nm) red light slows eye growth so that eyes remain hyperopic. We will test two hypotheses about the red-produced STOP signals that will not only improve our understanding of the emmetropization mechanism, but also will tell us if a form of this red stimulus has the potential to be developed as a method to slow myopia development in children. In specific aim 1 we will determine if the red light paradigm slows eye growth in juvenile tree shrews when used for as little as two hours per day and in older juvenile animals. In specific aim 2 we will determine if the red light paradigm can restrain the eye growth caused by wearing a minus lens, an established tool for inducing myopia in animals that may mimic human myopiagenic environments. We have also found (2) that ambient flickering short wavelength (464 ± 10 nm) blue light containing many temporal frequencies is strongly myopiagenic. Further, interactions of the red and blue is stimuli can negate the effects of the red light, producing myopia. In specific aim 3 we will examine the blue/red temporal interactions that stimulate myopia. These may identify components of artificial lighting that should be avoided. The data collected in the proposed grant will potentially lead to a further proposal as an RO1.

 描述（由申请人提供）：在出生后发育期间，当眼睛仍在生长时，通常称为正视化机制的机制使用眼睛的屈光不正来调节巩膜壳的生长，以匹配眼睛在焦平面上的轴向长度。当功能正常时，这种机制确保图像将清晰地聚焦在视网膜上。对于超过40%的美国人和高达96%的东亚群体来说，问题是眼睛变得太长，无法容纳自己的光学系统，因此近视。除了眼科检查、眼镜、隐形眼镜和屈光手术的费用（美国每年超过140亿美元）外，即使是少量的近视也会增加致盲的风险。因此，需要有效的策略来减缓眼睛生长并降低儿童青少年近视的患病率。 已经开发了各种策略（双焦点眼镜和接触镜、毒蕈碱拮抗剂滴眼液、巩膜加固手术）来控制轴向伸长和近视，但成功有限。一个重要的问题是，我们对正视化机制所使用的一个或多个视觉提示没有扎实的理解，以确定眼睛是否太短（远视）并且应该增加其生长速率以实现正视，或者眼睛是否变得太长（近视）并且应该减慢轴向伸长速率以匹配光学器件的成熟。我们已经开发了一种新的理论来解释视网膜是如何做到这一点的，这是基于光感受器和它们所连接的神经元所经历的焦点内与焦点外图像波动的时间特性。这使我们发现两种刺激对幼树鼩（一种与灵长类动物密切相关的锥细胞为主的二色视哺乳动物）的屈光发育具有强大的影响：（1）环境长波长（628 ± 10 nm）红光减缓眼睛生长，使眼睛保持远视。我们将测试关于红色产生的STOP信号的两个假设，这不仅将提高我们对正视化机制的理解，而且还将告诉我们这种红色刺激的形式是否有可能被开发为减缓儿童近视发展的方法。 在具体目标1中，我们将确定当每天使用两个小时的红光时，红光范例是否会减缓幼年树鼩和老年幼年动物的眼睛生长。 在具体目标2中，我们将确定红光范例是否可以抑制由佩戴负透镜引起的眼睛生长，负镜片是一种在动物中诱导近视的既定工具，可以模拟人类近视源性环境。 我们还发现（2）含有许多时间频率的短波长（464 ± 10 nm）蓝光具有强烈的近视源性。此外，红色和蓝色刺激的相互作用可以抵消红光的效果，产生近视。在具体目标3中，我们将研究刺激近视的蓝色/红色时间相互作用。这些可以识别应该避免的人工照明的组件。在拟议拨款中收集的数据可能会导致作为RO 1的进一步建议。