The goal of this project is to understand the visually-guided regulation of axial length in juvenile eyes. Evidence from animal models strongly suggests that visual signals are used to match the developing eye s length to its optical power to produce eyes that are in good focus (e.g., the eyes become emmetropic.) Some aspects of the visual images on the retina, such as the amount of hyperopic defocus, stimulates eyes to elongate. As young eyes move from hyperopia toward emmetropia, the visual stimulus for elongation is reduced and the axial elongation rate is slowed, keeping the retina in the focal plane. Visual/neural control of scleral extensibility may be a key component in regulating the elongation rate of mammalian eyes during emmetropization. Our studies in tree shrews (small mammals closely related to primates) have found that the extensibility of the sclera is regulated by the visual environment. The sclera becomes more extensible in eyes with an environmentally-induced increase in elongation rate and less extensible in eyes with a decreased elongation rate. A detailed understanding of the spatial location and temporal pattern of changes within the sclera is needed to 1) determine how specific changes in scleral components produce changes in extensibility, and 2) help define the latency and signaling pathway(s) by which signals of retinal origin reach the sclera via the choroid. There are two broad objectives for this project period: First, Specific Aim 1 is to better define the visual stimuli that increase and decrease axial elongation rate. This will be accomplished by manipulating and measuring the amount and sign of defocus during the development of induced myopia. Second, Specific Aims 2 and 3 are to understand in detail the remodeling of the scleral matrix that controls axial elongation, learning what changes, where the changes occur and when the changes occur relative to changes in the visual environment and changes in axial elongation.
Specific Aim 2 is to define and localize the specific changes in collagen and proteoglycans in the scleral extracellular matrix that occur during the development of induced myopia and during recovery from an induced myopia;
Specific Aim 3 is to measure the time-course and latency of changes in scleral fibroblast gene expression for synthesis and degradation of scleral extracellular matrix during the development of induced myopia and recovery. The proposed experiments will significantly advance our understanding of the mammalian emmetropization mechanism. This, in turn, will help us to learn how human eyes normally control their elongation, and how interactions with the visual environment can lead to myopia (nearsightedness) in children.
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