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The Role of Ambient Light on Dopamine Signaling and Myopia Susceptibility
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Dissertation
The Role of Ambient Light on Dopamine Signaling and Myopia Susceptibility
2019
Overview
Myopia, or nearsightedness, results in a blurred image of objects at a distance caused by an elongated eye. In recent decades rates of myopia prevalence have risen dramatically. The increases in myopia are likely due to environmental factors during childhood. Research into the growing myopia prevalence has led to new discoveries of how visual experience influences refractive development and myopia. Evidence in both clinical studies and animal models of myopia have indicated that bright light exposure during time outdoors can prevent myopic eye growth. However, the effect of a broad range of ambient light on myopia susceptibility had not been investigated. By housing mice in dim, intermediate, and bright light with and without lens defocus, I was able to test the effect of a wide range of ambient lighting to determine the role each plays on myopia susceptibility in the mouse model. My novel findings show that dim light, in addition to bright, is protective against myopia. To determine the retinal signaling mechanisms behind this protection, dopamine, which had previously been implicated as a “stop signal” in myopic eye growth, and proteins related to dopamine synthesis, packaging, uptake, and degradation were measured in myopic and control mice from each light level. My results show that dopamine dynamics are dependent on an interaction between ambient light and lens defocus. To determine the potential for dopamine to prevent myopia, I measured myopia susceptibility after either pharmacological or transgenic approaches to increasing endogenous dopamine. L-DOPA, a dopamine precursor, completely prevented form deprivation myopia in mice. The clinical applicability of these findings was investigated by analyzing light exposure data from a cohort of children. I showed that non-myopic children spend as much time in dim light as in bright light, supporting the potential of dim light to be used as a preventive therapy for myopia. Together, these findings reveal a more complex effect of ambient light and visual defocus on dopamine signaling and refractive eye growth. Furthermore, these data show that a broad range of ambient light is important for healthy ocular development.
Publisher
ProQuest Dissertations & Theses
Subject
ISBN
0438935578, 9780438935570
