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: 10480816
• 负责人: TIMOTHY J GAWNE
• 金额: $ 36.16万
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10480816
• 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; Persons; Pharmacological Treatment; Pharmacology; Phase; Phototherapy; Population; Prevalence; Primates; Process; Public Health; Recovery; Refractive Errors; Reporting; Research; Retina; 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.

在出生后发育期间，当眼睛仍在生长时，“正视化机制”使用 调节巩膜壳的生长以使眼轴长度与焦点相匹配 飞机尽管如此，在超过40%的美国人和高达96%的东亚群体中，眼睛变得太长 因为它有自己的光学系统，所以它是近视的。即使是少量的近视也会增加失明的风险 条件和屈光手术不会改变这一点。因此，有效的策略，以减缓眼睛的生长和 降低近视的患病率是必要的。 正视眼的维持是一个被忽视的研究领域。大多数近视儿童正视相对 正常，但随后不能在正视的较长维持阶段维持正视。我们 对树鼩（与灵长类动物密切相关的锥体主导的二色性哺乳动物）的研究表明， 保持正视是整个青春期的一个积极过程。眼睛是否变得太短 （远视），并应增加其生长速度，以维持正视（视网膜GO信号是必要的），或者是它 变得过长（近视），并应减慢轴向伸长率以维持正视（视网膜STOP 需要信号）。一个重要的问题是，我们没有一个坚实的理解视觉线索 由正视化机制用于产生STOP信号，该信号将防止眼睛变得太 久了在树鼩中，我们发现，暴露于窄带长波长（红色）光（仅 刺激长波长敏感（或LWS）锥细胞）似乎会产生STOP信号，减缓生长 在正视化的维持阶段。 在具体目标1中，我们将确定红光的最佳参数，以产生最大的 STOP信号，并了解红灯STOP信号是否显示非线性求和，类似于 产生STOP信号的其他刺激（近视散焦或间断负镜片佩戴）。 在具体的目标2中，我们将确定红灯“治疗”是否可以产生一致的STOP信号， 长时间处于正视化的维持阶段。我们也会研究红灯是否能 以类似于近视控制研究中使用的范例抵消负透镜的近视源性效应。 在具体目标3中，我们将同时分析视网膜多巴胺和视网膜中的基因表达， 视网膜后信号级联，以确定红灯STOP信号是否通过与其他信号相同的途径起作用。 停止刺激（如从诱导近视中恢复），或者如果路径是平行的和新的。 从这一项目中获得的知识不仅将产生关于联合国系统运作的关键数据， 正视机制在维持阶段，但也可能导致红色的发展 光作为一种新型的抗近视疗法。