PROJECT SUMMARY/ABSTRACT Soon after birth, most infants develop the optimal refractive error (i.e., “clinical” emmetropia) in both eyes that is maintained throughout childhood and into adult life. However, for reasons not currently understood, a significant and rapidly increasing proportion of the population develop myopia, or nearsightedness. Because of structural changes that take place as the eye becomes myopic, even low degrees of myopia pose a significant risk for multiple blinding conditions. As a consequence, myopia is now one of the leading causes of permanent visual impairment in the world. Additionally, myopia represents a substantial economic burden. In addition to lost productivity, billions of dollars are spent annually on optical corrections and pathologies caused by myopia. The long-term goal of our research program is to provide a better understanding of the etiology of common forms of myopia, juvenile and early adult onset myopia, and ultimately to develop effective treatment strategies that reduce the burden of myopia. The specific aims of our proposed research are to determine how visual experience affects refractive development, to characterize the operational properties of the vision-dependent mechanisms that regulate eye growth, and to explore new pharmaceutical approaches to eliminate myopia. Our purpose is to generate knowledge that can be applied to the human eye; however, many of the required experiments cannot be conducted in humans. Therefore, these experiments will be conducted using rhesus monkeys. Previous studies in our lab and others show that light/dark exposure patterns and characteristics of light, such as intensity and wavelength, influence eye growth. Potential mechanisms include alterations in circadian rhythm pathways and ocular remodeling, particularly of the sclera, the outermost coat of the eye. Preliminary data also show that prostaglandin analogs and alpha adrenergic agonists influence eye growth. Here, controlled rearing strategies, optical and biometric techniques, and histopathological investigation will be used to determine: 1) the effects of duration and time of day of red light exposure on eye growth and myopia and 2) whether prostaglandin analogs and alpha-2 adrenergic agonists can slow the development of myopia. The role of intraocular pressure, inflammation, and scleral remodeling in eye growth will be examined. The proposed experiments focus on fundamental issues concerning the manner in which visual experience influences refractive development. Findings will be important in determining how and to what extent visual experience contributes to the genesis of common human refractive errors. More importantly, the results of these studies will potentially provide the scientific foundation for qualitatively new treatment and management strategies for the most common forms of myopia. Findings will contribute the development of treatments to effectively slow the progression of myopia in children to increase quality of life, reduce the risk of associated pathologies, and decrease the economic burden caused by myopia.

PROJECT NARRATIVE Myopia, or nearsightedness, is a significant public health concern because, in addition to the high costs and the complications associated with traditional optical and surgical correction strategies, myopia can lead to permanent vision loss and ocular abnormalities causing blindness. Moreover, recent evidence suggests that the prevalence of myopia and, consequently, its impact are increasing rapidly. Hence, we aim to develop urgently needed treatment strategies to prevent and reduce the degree of myopia.