Retinal Mechanisms of Refractive Development

摘要 在过去的30年里，近视患病率的迅速增加表明环境在近视发病中的作用。 控制屈光发育。越来越多的证据表明，环境光（如阳光）会影响 儿童时期的眼睛发育是由多巴胺信号引起的。然而，视觉刺激的特征和 调节屈光发育的潜在视网膜信号仍然难以捉摸。在这份报告中，知识 关于环境辐照的视网膜“增益调节”途径是否会改变近视的差距 敏感性将得到解决。初步数据显示，昏暗和明亮的光线对透镜都有保护作用- 诱导小鼠近视，近视儿童在昏暗和明亮的光线下花费的时间更少。此外，委员会认为， 多巴胺活性受到暴露于可变环境照明的相互作用效应的不同调节 和透镜散焦。因此，假设视网膜对环境光的“增益调节”决定了视网膜对环境光的敏感性。 将测试生物体通过多巴胺信号传导对近视的易感性。有人提出，视网膜 辐照度的检测是通过非经典的视网膜通路发生的 在从星光到阳光的广泛环境条件下。该提案将决定 光感受器通路调节暗适应光和明适应光对透镜诱导近视的保护作用 和多巴胺信号的作用，通过使用小鼠模型追求三个特定的目标。目标1将评估是否 视杆通路刺激驱动多巴胺释放并降低昏暗和明亮下的近视屈光 环境条件。目的2将研究通过Cx 36间隙连接的视网膜传递是否提供保护性 通过增加多巴胺的释放，在昏暗和明亮的光线下对LIM产生影响。目标3将确定ipRGC是否 通过在全范围的环境条件下检测视觉刺激来调节屈光发展。的 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 近视眼生长的潜在机制预计这些成果将促进新的 为越来越多的近视儿童提供治疗干预。

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.