Myopia: the role of cone opsin mutations & glasses that control axial elongation

近视：视锥细胞视蛋白突变的作用

• 批准号: 8730660
• 负责人: Jay Neitz
• 金额: $ 42.63万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8730660
• 关键词: 11 year old; Address; Adolescence; Adult; Affect; Age; Alaska Native; Amino Acid Sequence; Asians; Birth; Blindness; Caring; Caucasians; Caucasoid Race; Characteristics; Child; Chinese People; Color; Cone; Cornea; Country; Cues; Data; Diagnosis; Ensure; Environment; Environmental Risk Factor; Eskimo Population; Ethnic Origin; Ethnic group; Etiology; Exposure to; Eye; Eye Part; Eyeglasses; Feedback; Genes; Genetic; Genetic Determinism; Glass; Goals; Grant; Growth; Haplotypes; Heritability; High Prevalence; Human; Image; Individual; Inherited; Intervention; Japanese Population; Lead; Length; Light; Measurement; Measures; Mechanical Stress; Mediating; Methods; Methyl Green; Mutation; Myopia; Native Americans; Normal Range; Opsin; Optics; Parents; Pathway interactions; Pattern; Photoreceptors; Pigments; Pilot Projects; Play; Population; Predisposition; Prevalence; Preventive; Process; Progressive Myopia; Quality of life; Reading; Refractive Errors; Relative (related person); Research; Retina; Retinal; Risk; Risk Factors; Role; Schools; Secondary to; Signal Transduction; Stimulus; Strategic Planning; Symptoms; Testing; Treatment Cost; Variant; Vision; Visual; Visual impairment; absorption; cost; emmetropization; ethnic difference; experience; falls; genetic variant; health disparity; improved; insight; lens; light intensity; mutant; prevent; programs; rare variant; research study; response; vision development; visual control

DESCRIPTION (provided by applicant): Myopia is a major problem worldwide with the number of affected individuals estimated to be as high as 90% for some Asian countries. The prevalence of myopia in the US is on the rise, up from 25% in 1971-1972 to 41.6% in1999-2004, with some underserved ethnic groups such as Native Americans and Alaskan Eskimos being particularly susceptible. The annual cost of treatment approximates 2-3 billion dollars for the estimated 40-50 million affected individuals in the US. In addition, myopia can lead to secondary complications that cause severely reduced vision. Myopia is caused both by genetic and environmental factors. Humans are normally born hyperopic, with eyes too short for the optics. During development, visual experience regulates eye growth so that the eye stops growing when the length is optimal for the optics (emmetropia). Myopia occurs when the eye grows past the point of emmetropia, becoming too long. The long- (L) and middle- (M) wavelength-sensitive cones mediate visually guided eye growth. Preliminary data is presented suggesting that 1) rare variants of the L and M cone opsin genes underlie a severe inherited form of myopia 2) there is an association between common myopia and variants of L and M opsin genes and 3) the L to M cone ratio influences visually guided eye growth. The L and M cone opsin genes are highly variable, encoding a tremendous amount of amino acid sequence variation in the opsins, making them excellent candidates for causing common forms of myopia. The ratio of L to M cones is also highly variable across individuals, which produces variability in the response of retinal circuits to environmental stimuli, which in turn influences eye growth. The involvement of the L/M cone pigments and cone ratio in the mechanism regulating eye growth suggests that axial elongation can be controlled by modifying visual experience. In a pilot study, children wore special eyeglasses containing one experimental and one control lens for three months. Both lenses had the individual's optimal correction. The experimental lens had a color-blocking filter to remove red light, and a holographic diffuser to blur the image slightly. The control lens passed red and green light equally but ensured that both eyes were exposed to the same light intensity throughout the study. Axial length measurements were taken at two week intervals. Eyes wearing the experimental treatment lens grew significantly slower than eyes wearing the control lens (p=0.001), making this a very promising method for preventing myopia. This application addresses the stated objective in NEI's Health Disparities Strategic Plan to "determine the etiology of human myopia and identify the risk factors associated with this and other refractive errors so as to prevent their occurrence or progression." Specific aim 1 will evaluate the role of cone ratio, axial length, and L and M cone opsin gene variants in the etiology of myopia. Aim 2 will investigate the role of L: M cone ratio in the etiology of myopia by comparing ratios across ethnic groups particularly at risk for myopia. Aim 3 will evaluate the potential of lenses that block specific wavelengths of light and introduce image blur in slowing axial elongation in myopic children.

描述（由申请人提供）：近视是全世界的一个主要问题，某些亚洲国家估计受影响的个体数量高达90％。美国近视的患病率正在上升，从1971 - 1972年的25％增加到1999年至2004年的41.6％，一些服务不足的族裔（如美洲原住民和阿拉斯加爱斯基摩人）特别容易受到影响。在美国估计受影响的人的年度治疗费用约为2-3亿美元。此外，近视可能会导致次要并发症，从而导致视力严重降低。近视是由遗传和环境因素引起的。人类通常天生的远视，眼睛太短，无法使用光学元件。在开发过程中，视觉体验调节眼睛的生长，因此当长度最佳的光学元件（Emmetropia）时，眼睛会停止生长。当眼睛长到艾米特罗迪亚的点，变得太长时，近视就会发生。长（L）和中（M）波长敏感的锥体介导视觉引导的眼睛生长。提出了初步数据表明1）L和M锥蛋白基因的罕见变体是近视的严重遗传形式的基础2）近视的严重遗传形式是共同的近视与L和M OPSIN基因的变体之间存在关联，而L和M锥形的比例为M锥形比率影响了视觉引导性眼睛生长。 L和M锥蛋白基因是高度可变的，编码了Opsins中大量的氨基酸序列变化，使其成为引起近视共同形式的极好候选者。 L与M锥的比率在各个个体之间也高度可变，这在视网膜电路对环境刺激的响应中产生可变性，这反过来又影响了眼睛的生长。 L/M锥色素和锥比在调节眼睛生长的机制中的参与表明，可以通过修饰视觉体验来控制轴向伸长。在一项试点研究中，儿童穿着特殊的眼镜，其中包含一个实验性和一个对照镜头三个月。这两个镜头都有个人的最佳校正。实验镜头具有一个颜色阻滞滤波器，可去除红光，并具有全息扩散器，以稍微模糊图像。对照镜头平均通过红色和绿光，但确保两只眼睛在整个研究过程中都暴露于相同的光强度。轴向长度测量以两周的间隔进行。穿着实验治疗镜头的眼睛比戴着对照镜头的眼睛变慢得多（p = 0.001），这使得这是预防近视的非常有前途的方法。该申请解决了NEI健康差异战略计划中既定的目标，以“确定人类近视的病因，并确定与此和其他屈光度错误相关的风险因素，从而防止其发生或进展。”具体目标1将评估锥形比，轴向长度以及L和M锥基因在近视病因中的作用。 AIM 2将通过比较族裔群体的比例，特别是近视风险，研究L：M锥比在近视的病因中的作用。 AIM 3将评估透镜阻断特定波长的镜头的潜力，并在减慢近视儿童的轴向伸长时引入图像模糊。