Retinal Mechanisms of Refractive Development

视网膜屈光发育机制

• 批准号: 10400053
• 负责人: Machelle T. Pardue
• 金额: $ 8.08万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10400053
• 关键词: Address; Adult; Affect; Automobile Driving; Cell physiology; Characteristics; Child; Childhood; Cone; Data; Detection; Development; Dopamine; Environment; Exposure to; Eye; Eye diseases; Fostering; Funding; Gap Junctions; Goals; Growth; Image; Intervention; Knock-out; Knowledge; Light; Lighting; Measurement; Measures; Mus; Myopia; Neuromodulator; Organism; Outcome; Pathway interactions; Photoreceptors; Photosensitivity; Population; Predisposition; Prevalence; Proteins; Reporting; Research; Retina; Retinal Ganglion Cells; Risk Factors; Rod; Role; Signal Pathway; Signal Transduction; Sunlight; Testing; Therapeutic Intervention; Time; Transgenic Mice; Vertebrate Photoreceptors; Vision; Visual; Wild Type Mouse; connexin 36; deprivation; designer receptors exclusively activated by designer drugs; effective therapy; experimental study; innovation; intervention effect; lens; mouse model; mutant; novel therapeutic intervention; prevent; protective effect; response; sensor; therapeutic development; transmission process; visual stimulus

Abstract The rapid increase in myopia prevalence over the last 30 years suggests a role for the environment in controlling refractive development. Accumulating evidence suggests that ambient light (e.g. sunlight) affects eye growth during childhood by dopamine signaling. However, the characteristics of visual stimuli and underlying retinal signals that regulate refractive development remain elusive. In this proposal, the knowledge gap concerning whether retinal “gain adjustment” pathways for ambient irradiance may alter myopia susceptibility will be addressed. Preliminary data shows that both dim and bright light are protective for lens- induced myopia in mice and that myopic children spend less time in both dim and bright light. Furthermore, dopamine activity is differentially modulated by an interaction effect of exposure to variable ambient lighting and lens defocus. Thus, the hypothesize that retinal “gain adjustment” to ambient light determines an organism’s susceptibility to myopia through dopamine signaling will be tested. It is proposed that retinal detection of irradiance occurs through non-classical retinal pathways that have been reported to detect light across a broad range of ambient conditions from starlight to sunlight. This proposal will determine which photoreceptor pathways modulate the protective effects of scotopic and photopic light on lens induced myopia and the role of dopamine signaling by pursuing three specific aims using mouse models. Aim 1 will evaluate if rod pathway stimulation drives dopamine release and decreases myopic refractions under dim and bright ambient conditions. Aim 2 will investigate if retinal transmission through Cx36 gap junctions provides protective effects for LIM in dim and bright light via increased dopamine release. Aim 3 will determine whether ipRGCs modulate refractive development by detecting visual stimuli under a full range of ambient conditions. The expected outcomes will increase our knowledge of basic retinal dopamine signaling and further elucidate the mechanisms underlying myopic eye growth. These results are expected to foster the development of new therapeutic interventions for the growing number of myopic children.

抽象的 过去30年中，近视患病率的迅速增加表明环境在 控制屈光开发。积累的证据表明，环境光（例如阳光）会影响 多巴胺信号传导在儿童时期的眼睛生长。但是，视觉刺激和 调节屈光作品的基本剩余信号仍然难以捉摸。在此提案中，知识 关于环境辐照度的视网膜“增益调整”途径是否可能改变近视的差距 敏感性将被解决。初步数据表明，昏暗和明亮的光受到镜头的保护 在小鼠中诱发的近视​​，近视儿童在昏暗和明亮的光线下花费的时间更少。此外， 通过暴露于可变环境照明的相互作用的效果，多巴胺的活性不同地调节 和镜头散焦。这就是假设残留的“增益调整”以确定 有机体通过多巴胺信号传导对近视的敏感性将进行测试。有人提出了视网膜 通过据报道检测光的非经典视网膜途径进行辐照的检测 从星光到阳光的广泛环境条件。该建议将确定哪个 光感受器的途径调节了Scotopic和Photopic Light对镜片诱导近视的受保护作用 以及使用小鼠模型追求三个特定目标，以及多巴胺信号传导的作用。 AIM 1将评估是否 杆途径刺激驱动多巴胺释放并减少昏暗和明亮的近视折射 环境条件。 AIM 2将调查是否通过CX36间隙连接永久传输提供受保护的 通过增加的多巴胺释放，在昏暗和明亮的光中对LIM的影响。 AIM 3将确定IPRGC是否 通过在整个环境条件下检测视觉刺激来调节折射的发育。 预期的结果将增加我们对基本视网膜多巴胺信号传导的了解，并进一步阐明 近视生长的机制。这些结果有望促进新的发展 近视儿童数量越来越多的治疗干预措施。