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
基本信息
- 批准号:8186141
- 负责人:
- 金额:$ 36.46万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:11 year oldAddressAdolescenceAdultAffectAgeAlaska NativeAmino Acid SequenceAsiansBirthBlindnessCaringCaucasiansCaucasoid RaceCharacteristicsChildChinese PeopleColorCorneaCountryCuesDataDiagnosisEnsureEnvironmentEnvironmental Risk FactorEskimo PopulationEthnic OriginEthnic groupEtiologyExposure toEyeEye PartEyeglassesFeedbackGenesGeneticGenetic DeterminismGenetic VariationGlassGoalsGrantGrowthHaplotypesHeritabilityHigh PrevalenceHumanImageIndividualInheritedInterventionJapanese PopulationLeadLengthLightMeasurementMeasuresMechanical StressMediatingMethodsMethyl GreenMutationMyopiaNative AmericansNormal RangeOpsinOpticsParentsPathway interactionsPatternPhotoreceptorsPigmentsPilot ProjectsPlayPopulationPredispositionPrevalencePreventiveProcessProgressive MyopiaQuality of lifeReadingRefractive ErrorsRelative (related person)ResearchRetinaRetinalRetinal ConeRiskRisk FactorsRoleSchoolsSecondary toSignal TransductionStimulusStrategic PlanningSymptomsTestingTreatment CostVariantVisionVisualVisual impairmentabsorptioncostemmetropizationethnic differenceexperiencefallshealth disparityimprovedinsightlenslight intensitymutantpreventprogramsresearch studyresponsevision developmentvisual control
项目摘要
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(申请人提供):近视是世界范围内的一个主要问题,在一些亚洲国家,近视患者的数量估计高达90%。近视在美国的流行率正在上升,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尤其容易受到影响。在美国,估计有4000-5000万受影响的个人,每年的治疗费用约为20-30亿美元。此外,近视可能会导致继发性并发症,导致严重的视力下降。近视既有遗传因素,也有环境因素。人类通常生来就有远视,眼睛太短,不能戴眼镜。在发育过程中,视觉经验调节眼睛的生长,这样当眼睛的长度对光学系统(正视)来说是最佳时,眼睛就停止生长。当眼睛超过正视点,变得太长时,就会发生近视。长(L)和中(M)波长敏感的视锥细胞调节视觉引导的眼睛生长。初步数据表明:1)L视锥蛋白基因和M视锥蛋白基因的罕见变异是一种严重的遗传性近视的基础;2)常见的近视与L和M视蛋白基因的变异有关;3)L视锥与M视锥细胞的比例影响视觉引导眼的生长。L和M视锥视蛋白基因高度可变,编码视蛋白中大量的氨基酸序列变化,使它们成为导致常见形式近视的极佳候选基因。L和M视锥细胞的比例在不同个体之间也是高度不同的,这会导致视网膜回路对环境刺激的反应发生变化,进而影响眼睛的生长。L/M视锥细胞色素和视锥细胞比率参与了眼球生长的调节机制,提示轴向伸长可以通过改变视觉体验来控制。在一项初步研究中,孩子们戴了三个月的特殊眼镜,其中包括一个实验镜片和一个对照镜片。两种镜片都有个人的最佳矫正效果。实验镜头有一个滤色器来去除红光,还有一个全息漫射器来使图像略微模糊。控制镜片的红光和绿光的透过率相同,但确保在整个研究过程中双眼暴露在相同的光强度下。每隔两周测量一次眼轴长度。戴实验性治疗镜片的眼睛比戴对照镜片的眼睛生长明显慢(p=0.001),这使这成为一种非常有希望的预防近视的方法。该应用程序解决了NEI的健康差异战略计划中所述的目标,即“确定人类近视的病因,并确定与该屈光不正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中的作用。目的2通过比较近视高危人群间的视锥比,探讨L:M视锥比在近视病因中的作用。目标3将评估阻挡特定波长的光的镜片的潜力,并在减缓近视儿童的轴向延长方面引入图像模糊。
与公共健康相关:近视在美国的流行率正在上升,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尤其容易受到影响。据估计,美国约有4000万至5000万受近视影响的个人,每年的治疗费用约为20-30亿美元,此外,近视可能导致严重损害视力的继发性并发症。这笔赠款的主要目标是研究近视病因中新发现的基因和环境线索,并建立一种新确定的治疗方法,在一项小型先导性研究中,这种方法显示出巨大的前景,是一种有效、廉价、非侵入性、非药物手段,可以减缓或阻止异常的眼睛生长。
项目成果
期刊论文数量(0)
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Jay Neitz其他文献
Jay Neitz的其他文献
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{{ truncateString('Jay Neitz', 18)}}的其他基金
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:
8541020 - 财政年份:2011
- 资助金额:
$ 36.46万 - 项目类别:
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:
8328609 - 财政年份:2011
- 资助金额:
$ 36.46万 - 项目类别:
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 - 财政年份:2011
- 资助金额:
$ 36.46万 - 项目类别:
Functional Analysis of the Visual System and In Vivo Ocular Imaging Module
视觉系统和体内眼部成像模块的功能分析
- 批准号:
10693862 - 财政年份:1997
- 资助金额:
$ 36.46万 - 项目类别:
Systems Biology Services and Shared Instrumentation
系统生物学服务和共享仪器
- 批准号:
10006557 - 财政年份:1997
- 资助金额:
$ 36.46万 - 项目类别:
Functional Analysis of the Visual System and In Vivo Ocular Imaging Module
视觉系统和体内眼部成像模块的功能分析
- 批准号:
10471349 - 财政年份:1997
- 资助金额:
$ 36.46万 - 项目类别:
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