Effects of wavelength on achieving and maintaining emmetropia

波长对实现和维持正视眼的影响

• 批准号: 9769049
• 负责人: TIMOTHY J GAWNE
• 金额: $ 37.27万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9769049
• 关键词: Address; Adolescence; Adolescent; Adult; Affect; Age; American; Animal Experimentation; Animals; Area; Blindness; Cataract; Characteristics; Child; Choroid; Clinical Treatment; Cone; Cues; Data; Development; Dimensions; Distant; Dopamine; Exposure to; Eye; Failure; Far East; Feedback; Gene Expression; Gene Expression Profile; Glaucoma; Growth; Human; Hyperopia; Image; Interruption; Knowledge; Lead; Learning; Length; Light; Maintenance; Mammals; Measures; Messenger RNA; Modeling; Myopia; Operative Surgical Procedures; Optics; Pathway interactions; Pharmacological Treatment; Pharmacology; Phase; Phototherapy; Population; Prevalence; Primates; Process; Public Health; Recovery; Refractive Errors; Reporting; Research; Retina; Retinal; Retinal Perforations; Risk; Risk Factors; Signal Transduction; Solid; Stimulus; System; Testing; Time; Translating; Tupaiidae; Visual; Work; effective therapy; emmetropization; lens; mRNA Expression; neglect; nonhuman primate; novel; operation; postnatal development; prevent; tool; treatment strategy; ward

During postnatal development when the eye is still growing, an “emmetropization mechanism” uses the eye’s refractive error to regulate the growth of the scleral shell to match the axial length of the eye to the focal plane. Despite this, in over 40% of Americans and up to 96% of groups in East Asia, the eye becomes too long for its own optics and is thus myopic. Even low amounts of myopia raise the risk of developing blinding conditions and refractive surgery does not change this. Thus, effective strategies to slow eye growth and reduce the prevalence of myopia are needed. Maintenance of emmetropia is a neglected area of research. Most myopic children emmetropize relatively normally, but then are unable to maintain emmetropia in the longer maintenance phase of emmetropia. Our research in tree shrews (cone-dominated dichromatic mammals closely related to primates) has shown that maintaining emmetropia is an active process throughout adolescence. Is the eye becoming too short (hyperopia) and should increase its growth rate to maintain emmetropia (retinal GO signals are needed), or is it becoming too long (myopia) and should slow the axial elongation rate to maintain emmetropia (retinal STOP signals are needed). An important problem is that we do not have a solid understanding of the visual cues used by the emmetropization mechanism to generate STOP signals that will prevent eyes from becoming too long. In tree shrews, we have discovered that exposure to narrow-band long wavelength (red) light (which only stimulates the long-wavelength sensitive, or LWS, cones) seems to generate STOP signals that slow growth during the maintenance phase of emmetropization. In specific aim 1, we will determine the optimal parameters for the red light to generate the maximum STOP signal with minimal exposure and learn if red-light STOP signals show non-linear summation, similar to other stimuli that generate STOP signals (myopic defocus or interrupted minus-lens wear). In specific aim 2, we will determine if the red light “treatment” can produce consistent STOP signaling over a long period of time in the maintenance phase of emmetropization. We will also examine if the red light can counteract the myopiagenic effects of a minus lens in a paradigm similar to that used in myopia-control studies. In specific aim 3, we will use both analysis of retinal dopamine, and of gene expression in the retina and post-retinal signaling cascade, to determine if red-light STOP signals act via the same pathways as other STOP stimuli (such as recovery from induced myopia), or if the pathways are parallel and novel. The knowledge gained from this project will not only generate critical data on the operation of the emmetropization mechanism during the maintenance phase, but also may result in the development of red light as a novel anti-myopia therapy.

在产后发育期间，当眼睛仍在生长时，“弹药机制”使用 眼睛的折射误差以调节巩膜壳的生长以使眼睛的轴向长度与焦点相匹配 飞机。尽管如此，在东亚超过40％的美国人和多达96％的群体中，眼睛变得太长了 为了自己的光学，因此是近视。即使近视也很少，也会增加患盲的风险 病情和屈光手术不会改变这一点。那，有效的策略来减缓眼睛的生长和 需要减少近视的患病率。 维持Emmetropia是一个被忽视的研究领域。大多数近视儿童相对蒙盖 通常，但随后无法在Emmetropia的较长维持阶段维持Emmetropia。我们的 树sh的研究（锥体主导的二分法哺乳动物与私人密切相关）表明 维持Emmetropia是整个青少年的活跃过程。眼睛变得太短了吗 （远视），并应提高其维持艾米特罗比亚的生长速度（需要视网膜GO信号），或者是 变得太长（近视），应该减慢轴向伸长率维持艾米特罗皮亚（视网膜停止 需要信号）。一个重要的问题是，我们对视觉提示没有可靠的理解 通过弹药机制使用来产生停止信号，以防止眼睛变得 长的。在Tree Shrews中，我们发现暴露于窄带长波长（红色）光线（只有 刺激长波长敏感或LWS的锥体似乎会产生停止信号，从而缓慢生长 在弹性化的维护阶段。 在特定目标1中，我们将确定红灯的最佳参数以生成最大值 停止信号的曝光最少，并了解红灯停止信号是否显示非线性求和，类似于 产生停止信号的其他刺激（近视散热器或中断负镜头磨损）。 在特定目标2中，我们将确定红灯“处理”是否可以产生一致的停止信号 在弹性化的维护阶段长期存在。我们还将检查红灯是否可以 抵消了与近视控制研究相似的范式中减去镜头的肌关节作用。 在特定目标3中，我们将使用视网膜多巴胺的分析和视网膜中的基因表达和基因表达 视网膜后信号级联，以确定红灯停止信号是否通过与其他相同的途径作用 停止刺激（例如从诱导的近视中恢复），或者如果途径是平行且新颖的。 从该项目中获得的知识不仅会生成有关操作的关键数据 维护阶段的弹性化机制，但也可能导致红色的发展 光作为一种新型的抗果皮疗法。