The sclera, a connective tissue consisting of collagen and proteoglycans, provides the structural integrity that defines the shape and length of the eye. This proposal examines the hypothesis that myopia, a common abnormal visual condition characterized by lengthening of the posterior eye globe, is a connective tissue disorder in which the scleral matrix components are inappropriately remodeled. The objective of this proposal is to characterize the biochemical events within the sclera that produce ocular elongation and to identify regulatory mechanisms that govern these changes. The well established chick model of form deprivation myopia will be used to determine whether: 1) form deprivation stimulates the transcription and/or the translation of proteoglycans by scleral chondrocytes -- changes in proteoglycan syn- thesis will be evaluated in scleral cell culture using probes for glycosaminoglycan, core protein and mRNA; 2) alterations in scleral collagens occur during ocular enlargement -- comparisons will be made between normal and myopic sclera on collagen morphology by TEM, collagen crosslinking by acid extraction with and without pepsin, collagen types by selective salt precipitation, and collagen synthesis in cell culture; 3) changes in ocular size and shape are due to regional remodeling of the sclera matrix -- the synthesis and deposition of proteoglycans will be compared in normal and myopic sclera using autoradiography and the rate of turnover of scleral collagen and proteoglycans will be deter- mined by assessing the regional activity of matrix-degrading metallo- proteinases; 4) a soluble factor produced within the eye initiates the changes in scleral matrix -- the ability of known growth factors to stimulate proteoglycan synthesis by scleral cells in culture will be tested and their distribution in ocular tissues will be measured using immunoassays. The long range goal is to apply these results to the improved understanding of myopia and prevention of blindness due to retinal detachment and degeneration.
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