Myopia (nearsightedness) is on the rise around the world and in the United States. It affects tens of millions of Americans and, in progressive forms, is a leading cause of blindness. Earlier research with humans and experimental animal models has made it clear that the postnatal development of the eye and refractive state involves a combination of genetic and visual factors. The rise in incidence of human myopia has been associated with increases in literacy and levels of education, although the nature of the relationship is unclear. Research using animal models has established that visual stimuli related to retinal defocus regulate eye growth and refractive state. The studies described in this proposal use various visual manipulations to explore the temporal integration of visual stimuli that affect eye growth and the biochemical mechanisms that may underlie these changes. The following questions are asked: (1) How does the eye temporally integrate different visual stimuli for the regulation of eye growth? To answer this, the investigators will contrast the effects of different states of defocus or deprivation with corrected or clear vision and examine the stimulus durations necessary to elicit different ocular growth responses. (2) Do ocular circadian rhythms in IOP, axial length and choroid thickness play a role in the regulation of ocular growth? Specifically, the investigators will examine the phase relationships between these different rhythms during induced changes in ocular growth rate. (3) How do the temporal pattern and accuracy of accommodation affect the degree of blur experienced during near work tasks and when viewing through negative power spectacle lenses? These measures of accommodative behavior will then be correlated with the degree of experimental myopia induced. (4) What are the changes in scleral extracellular matrix during experimentally induced changes in ocular growth, and how are they controlled? Using ocular tissues from the other experiments, the investigators will quantify changes in scleral extracellular components and correlate them with visually induced increases and decreases in ocular growth rate. In addition, the possibility that retinoic acid synthesis by the choroids/RPE plays a role in the signal cascade from retina to sclera will be explored. This project will bring together several lines of investigation to help answer important questions relating to how myopia develops in response to altered visual experience. These studies will provide new information for understanding the association of near work, such as reading, and the development of myopia in humans.
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