Retinal Mechanisms of Refractive Development

摘要 近视患病率在过去30年中的快速增长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 儿童时期眼睛发育受多巴胺信号的影响。然而，视觉刺激的特点和 调节屈光发育的潜在视网膜信号仍然难以捉摸。在这份提案中，我们知道 视网膜对环境辐射的“增益调节”通路是否会改变近视的差距 将解决易感性问题。初步数据显示，暗光和强光都对晶状体有保护作用。 在小鼠中，近视儿童在昏暗和明亮的光线下花费的时间更少。此外， 多巴胺活性受暴露于不同环境照明的交互作用的不同调节 和镜头散焦。因此，视网膜对环境光“增益调节”的假设决定了 将测试生物体通过多巴胺信号对近视的敏感性。有人建议，视网膜 对辐照度的检测是通过已报道的检测光的非经典视网膜通路进行的 在从星光到阳光的广泛环境条件下。这份提案将决定 光感受器通路调节暗视光和明视光对晶状体诱导近视的保护作用 以及利用小鼠模型通过追求三个特定目的来研究多巴胺信号的作用。AIM 1将评估是否 暗淡和明亮条件下刺激视杆通路可促进多巴胺释放并减少近视屈光度 周围环境条件。Aim 2将研究视网膜通过Cx36缝隙连接传递是否提供保护 在暗光和强光下通过增加多巴胺释放对LIM的影响。目标3将确定ipRGC是否 通过在各种环境条件下检测视觉刺激来调节屈光发育。这个 预期的结果将增加我们对基本视网膜多巴胺信号的了解，并进一步阐明 近视眼球发育的机制。这些成果有望促进新技术的发展 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.