Ocular diurnal rhythms and eye growth

描述（由申请人提供）：在美国，近视影响近25%的人口，而在某些其他发达国家，受影响的人口比例增加到80%或更多。病理性近视也是导致失明的主要原因。因此，了解调节眼睛生长的机制对于理解发展屈光不正的眼睛如何以及为什么会出错至关重要，并可能导致新疗法的开发。 最近的研究表明，眼球生长速率的变化与眼球昼夜节律的改变有关。本文提出的工作旨在扩展这些原始观察，以更好地理解这些影响的机制。具体来说，我们问是否相移的节奏在轴长和脉络膜厚度（两眼昼夜节律的相位已被证明是改变的视觉操作，改变生长速度）是时间相关的视觉诱导的变化率的眼睛生长。这意味着脉络膜厚度的变化可能在眼生长调节中起因果作用。为了进一步探讨这一概念，我们将测试的假设，每天短暂的变化脉络膜厚度的一部分，信号通路介导正视化。具体来说，我们问是否调解脉络膜厚度的变化和那些调解眼睛生长速度的变化的视觉信号是相同的，或分开。最后，我们将着眼于一些视觉和化学作用的昼夜节律在巩膜蛋白聚糖合成，以进一步探讨如何这些眼节律的阶段可能相互作用，在调节眼睛的生长。我们还将检验脉络膜视黄酸合成存在昼夜节律的假设，这可能影响巩膜蛋白多糖合成的昼夜节律。这三个目的的结果将使我们更接近于理解眼睛生长调节的分子机制，并阐明脉络膜在这些机制中的影响。

DESCRIPTION (provided by applicant): In the United States, myopia affects nearly 25 percent of the population, while in certain other developed countries the proportion of the population affected increases to 80 percent or more. Pathological myopia is also a leading cause of blindness. Therefore, understanding the mechanisms underlying the regulation of ocular growth is critical towards understanding how and why it goes awry in eyes that develop ametropias, and might lead to the development of new therapies. Recent work has indicated that changes in the rate of ocular growth are associated with alterations in ocular circadian rhythms. The work proposed here seeks to extend these original observations, to better understand the mechanisms underlying these effects. Specifically, we ask whether the phase shifts in the rhythms in axial length and choroid thickness (two ocular circadian rhythms the phases of which have been shown to be altered by visual manipulations that alter growth rate) are temporally correlated with visually induced changes in rate of ocular growth. This would imply that the changes in thickness of the choroid might play a causal role in ocular growth regulation. To further explore this notion we will test the hypothesis that daily transient changes in choroidal thickness are part of the signal pathway mediating emmetropization. Specifically, we ask whether the visual signals mediating changes in choroidal thickness and those mediating changes in ocular growth rate are the same, or are separate. Finally, we will look at some visual and chemical effects on the circadian rhythm in scleral proteoglycan synthesis to further explore how the phases of these ocular rhythms might interact in regulating ocular growth. We will also test the hypothesis that there is a diurnal rhythm in choroidal retinoic acid synthesis that might influence the diurnal rhythm in scieral proteoglycan synthesis. The results from these three Aims will bring us closer to understanding the molecular mechanisms underlying ocular growth regulation, and elucidate the influence of the choroid in these mechanisms.