Myopia is the most common of all ocular problems, affecting 25 percent of the US adult population. The most common structural abnormality associated with myopia is excessive lengthening of the posterior segment of the ocular globe (axial myopia). While it is clear that changes in the shape of the sclera produce myopia, the basis for this shape change is largely unknown. The sclera is a connective tissue, consisting of interwoven collagen fibrils in close association with proteoglycans that provides the structural framework that defines the shape and therefore the axial length of the eye. Past work by our lab and others has clearly demonstrated that the sclera is not a static container of the eye, but rather is a dynamic tissue, capable of altering extracellular matrix composition and its biomechanical properties in response to changes in the visual environment to regulate ocular size and refraction. The mechanism by which this visually-guided scleral remodeling is regulated is largely unknown. Preliminary data is presented in this proposal that implicates the choroid in the regulation of scleral metabolism. We hypothesize that changes in choroidal vascular permeability are responsible for the release of soluble factors that act on the sclera to regulate scleral proteoglycan synthesis and the rate of ocular elongation during visually guided ocular growth. Experiments outlined in the current application combine whole animal, cellular and molecular approaches to determine whether: 1) Changes in choroidal permeability correlate with the rate of scleral proteoglycan synthesis and rate of ocular elongation in chicks during visually guided ocular growth, 2) changes in scleral proteoglycan synthesis that occur during the development of form deprivation myopia (FDM), recovery from FDM, and during compensation for myopic and hyperopic defocus are regulated by changes in the composition of suprachoroidal fluid, and 3) ocular growth changes associated with the development of FDM, recovery from FDM and during compensation for myopic and hyperopic defocus are mediated by changes in choroidal gene expression. Results obtained from these studies will provide new information on choroidal function and cell biology, and provide insights into a novel mechanism of ocular growth regulation. Ultimately, this information may be applied to strategies to reverse or prevent the scleral extracellular matrix changes associated with myopia development. ? ? ?

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Central Visual Processing Study Section (CVP)
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Wujek, Jerome R
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University of Oklahoma Health Sciences Center
Anatomy/Cell Biology
Schools of Medicine
Oklahoma City
United States
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Harper, Angelica R; Le, Anh T; Mather, Timothy et al. (2018) Design, synthesis, and ex vivo evaluation of a selective inhibitor for retinaldehyde dehydrogenase enzymes. Bioorg Med Chem 26:5766-5779
Harper, Angelica R; Wang, Xiang; Moiseyev, Gennadiy et al. (2016) Postnatal Chick Choroids Exhibit Increased Retinaldehyde Dehydrogenase Activity During Recovery From Form Deprivation Induced Myopia. Invest Ophthalmol Vis Sci 57:4886-4897
Summers, Jody A; Harper, Angelica R; Feasley, Christa L et al. (2016) Identification of Apolipoprotein A-I as a Retinoic Acid-binding Protein in the Eye. J Biol Chem 291:18991-9005
Harper, Angelica R; Wiechmann, Allan F; Moiseyev, Gennadiy et al. (2015) Identification of active retinaldehyde dehydrogenase isoforms in the postnatal human eye. PLoS One 10:e0122008
Harper, Angelica R; Summers, Jody A (2015) The dynamic sclera: extracellular matrix remodeling in normal ocular growth and myopia development. Exp Eye Res 133:100-11
Summers, Jody A (2013) The choroid as a sclera growth regulator. Exp Eye Res 114:120-7
Rada, Jody A Summers; Hollaway, Lindsey R; Lam, Wengtse et al. (2012) Identification of RALDH2 as a visually regulated retinoic acid synthesizing enzyme in the chick choroid. Invest Ophthalmol Vis Sci 53:1649-62
Summers Rada, Jody A; Hollaway, Lindsey R (2011) Regulation of the biphasic decline in scleral proteoglycan synthesis during the recovery from induced myopia. Exp Eye Res 92:394-400
Rada, Jody A Summers; Wiechmann, Allan F; Hollaway, Lindsey R et al. (2010) Increased hyaluronan synthase-2 mRNA expression and hyaluronan accumulation with choroidal thickening: response during recovery from induced myopia. Invest Ophthalmol Vis Sci 51:6172-9
Wiechmann, Allan F; Hollaway, Lindsey R; Rada, Jody A Summers (2009) Melatonin receptor expression in Xenopus laevis surface corneal epithelium: diurnal rhythm of lateral membrane localization. Mol Vis 15:2384-403

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