Ocular diurnal rhythms and eye growth

描述(申请人提供)：在美国，近视影响了近25%的人口，而在某些其他发达国家，受近视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，了解眼睛生长调节的机制对于了解屈光不正的眼睛是如何以及为什么会出现问题至关重要，并可能导致新的治疗方法的开发。 最近的研究表明，眼球生长速度的改变与眼球昼夜节律的改变有关。这里提出的工作试图扩展这些最初的观察结果，以更好地理解这些效应背后的机制。具体地说，我们询问眼轴长度和脉络膜厚度的节律(这两个眼球昼夜节律的相位已经被证明可以通过改变生长速度的视觉操作来改变)的相移是否与视觉诱导的眼生长速度的变化在时间上相关。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。为了进一步探索这一概念，我们将检验这一假设，即每天脉络膜厚度的瞬时变化是调节正视化的信号通路的一部分。具体地说，我们问的是，调节脉络膜厚度变化的视觉信号和调节眼睛生长速度变化的视觉信号是相同的，还是不同的。最后，我们将观察在巩膜蛋白多糖合成中对昼夜节律的一些视觉和化学影响，以进一步探索这些眼球节律的相位如何在调节眼睛生长中相互作用。我们还将验证脉络膜维甲酸合成存在昼夜节律的假设，这可能会影响坐骨神经蛋白多糖合成的昼夜节律。这三个目标的结果将使我们更深入地了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.