Control of refractive development with temporally modulated light

 描述(申请人提供)：在眼睛还在生长的出生后发育过程中，一种通常被称为正视化机制的机制利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，这一机制确保图像将明显聚焦在视网膜上。对于超过40%的美国人和高达96%的东亚群体来说，问题是眼睛太长了，不适合自己的光学装置，因此是近视。除了眼科检查、眼镜、隐形眼镜和屈光手术的费用(在美国每年超过140亿美元)外，即使是少量近视也会增加患盲症的风险。因此，需要采取有效的策略来减缓眼睛的生长，降低儿童青少年近视的患病率。各种策略(双焦点眼镜和隐形眼镜，毒碱拮抗剂眼药水，巩膜加固术)已经被开发出来控制眼轴延长和近视，但收效甚微。一个重要的问题是，我们对正视化机制用来确定眼睛是否太短(远视)并应增加其生长速度以实现正视，或者眼睛是否变得太长(近视)并应减缓轴向延长率以匹配光学成熟的视觉线索没有确切的理解。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，这是基于光感受器及其连接的神经元经历的聚焦与散焦图像波动的时间特征。这导致我们发现了两种刺激对幼年树鼠的屈光发育有强大的影响，树鼠是一种锥体主导的二色哺乳动物，与灵长类动物关系密切：(1)环境长波(628±10 nm)红光减缓眼睛生长，使眼睛保持远视。我们将测试两个关于红色产生的停止信号的假设，这不仅将提高我们对正视化机制的理解，还将告诉我们，这种红色刺激的一种形式是否有潜力被开发为一种减缓儿童近视发展的方法。在特定的目标1中，我们将确定红光模式是否会减缓幼年树鼠每天使用两个小时的眼睛生长速度，并在年长的幼年动物中使用。在具体目标2中，我们将确定红光范例是否可以抑制因佩戴负透镜而导致的眼睛生长，负透镜是一种公认的工具，用于诱导动物近视，可能模仿人类的近视环境。我们还发现(2)包含许多时间频率的环境闪烁短波长(464±10 nm)蓝光具有很强的近视诱导性。此外，红色和蓝色刺激的相互作用会抵消红光的影响，从而产生近视。在具体目标3中，我们将研究刺激近视的蓝/红时间相互作用。这些信息可以确定应避免使用的人工照明组件。拟议拨款中收集的数据可能会导致另一项作为RO1的提案。

 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.