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: 8186141
• 负责人: Jay Neitz
• 金额: $ 36.46万
• 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/8186141
• 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; 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; Genetic Variation; 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; Retinal Cone; 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; health disparity; improved; insight; lens; light intensity; mutant; prevent; programs; 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. PUBLIC HEALTH RELEVANCE: 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 severely impair vision. The major objectives of this grant are to investigate newly identified genes and environmental cues in the etiology of nearsightedness and to establish a newly identified treatment that, in a small pilot study, showed great promise as an effective, inexpensive, non-invasive, non-pharmacological means of slowing or stopping abnormal eye growth.

描述（由申请人提供）：近视是全球范围内的一个主要问题，在一些亚洲国家，受影响的人数估计高达90%。近视在美国的患病率正在上升，从1971-1972年的25%上升到1999 -2004年的41.6%，一些服务不足的种族群体，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，估计有4000万至5000万受影响的个人，每年的治疗费用约为20亿至30亿美元。此外，近视可导致继发性并发症，导致视力严重下降。近视是由遗传和环境因素引起的。人类通常是天生的远视，眼睛太短的光学。在发育过程中，视觉经验调节眼睛的生长，使眼睛停止生长时，长度是最佳的光学（正视）。当眼睛长过正视点，变得太长时，就会发生近视。长（L）和中（M）波长敏感的视锥介导视觉引导的眼睛生长。初步数据表明：1）L和M视锥细胞视蛋白基因的罕见变体是严重遗传性近视的基础; 2）常见近视与L和M视蛋白基因的变体之间存在关联; 3）L与M视锥细胞比率影响视觉引导的眼睛生长。L和M视锥视蛋白基因是高度可变的，编码视蛋白中的大量氨基酸序列变异，使它们成为引起常见形式的近视的极好候选者。L与M视锥的比率在个体之间也是高度可变的，这在视网膜回路对环境刺激的响应中产生可变性，这反过来又影响眼睛的生长。L/M锥色素和锥比参与调节眼睛生长的机制表明，可以通过改变视觉体验来控制轴向伸长。在一项初步研究中，孩子们戴着一副实验用和对照用透镜的特殊眼镜，持续三个月。两种镜片均具有个体的最佳矫正。实验用的透镜有一个阻色滤光片来去除红光，还有一个全息漫射器来使图像稍微模糊。对照透镜可同等地通过红光和绿色光，但确保在整个研究期间双眼暴露于相同的光强度。每隔两周进行轴向长度测量。佩戴实验治疗透镜的眼睛比佩戴对照透镜的眼睛生长显著更慢（p=0.001），使得这是一种非常有希望的预防近视的方法。该申请解决了NEI的健康差异战略计划中规定的目标，即“确定人类近视的病因，并确定与此和其他屈光不正相关的风险因素，以防止其发生或发展。“具体目标1将评估视锥比、眼轴长度以及L和M视锥视蛋白基因变异在近视病因学中的作用。目的2将通过比较不同种族人群（尤其是有近视风险的人群）的L：M视锥比，研究L：M视锥比在近视病因学中的作用。目标3将评价镜片阻挡特定波长的光并引入图像模糊以减缓近视儿童眼轴伸长的潜力。 公共卫生相关性：近视在美国的患病率正在上升，从1971-1972年的25%上升到1999 -2004年的41.6%，一些服务不足的种族群体，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，估计有4000万至5000万受影响的个体，每年的治疗费用约为20亿至30亿美元，此外，近视可导致严重损害视力的继发性并发症。这项资助的主要目的是研究新发现的近视病因学基因和环境线索，并建立一种新发现的治疗方法，在一项小型试点研究中，这种方法作为一种有效、廉价、非侵入性、非药理学的手段，可以减缓或阻止眼睛的异常生长。