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.
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