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J.T. Siegwart, J.D. Robertson, T.T. Norton; Changes in MMP and TIMP mRNA Levels During Minus Lens Treatment and During Recovery in Tree Shrew . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1232.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To examine the time course of changes in matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) mRNA levels in tree shrew sclera during the development of experimentally induced myopia and during recovery. Methods: Competitive RT–PCR was used to measure the levels of mRNA for MT1–MMP (membrane type MMP1), MMP–2 (gelatinase–A), MMP–3 (stromelysin–1), TIMP–1, TIMP–2, and TIMP–3 in the scleras of normal tree shrews (24, 28, 35, or 39 days of visual experience [VE]), tree shrews that received 1, 2, 4, or 11 days of monocular –5D lens treatment starting at 24 days of VE, and tree shrews that received 2 or 4 days of recovery after 11 days of –5D lens wear (n=5/group). Awake, non–cycloplegic refractive measures (Nidek autorefractor) and A–scan ultrasonography under anesthesia were performed before and after treatment. Results: There was evidence for regulation of the levels of all six mRNAs studied. Differential Regulation: MT1–MMP and MMP–2 mRNA levels initially increased and then returned toward normal in the treated eye during minus lens wear. TIMP–3 mRNA levels decreased and then returned toward normal in the treated eye during minus lens wear. Co–regulation: TIMP–1 and TIMP–2 mRNA levels decreased slightly in both eyes during lens wear. The mRNA levels of all three TIMPs initially spiked upward in both eyes (after two days of Recovery) and then returned toward normal levels (after four days of Recovery.) MMP–3 mRNA levels showed an initial, transient increase in both eyes during minus lens treatment and during Recovery. Conclusions: These data provide further evidence that modulation of MMP and TIMP scleral gene expression plays a role in the scleral remodeling and modulation of the mechanical properties of the sclera that occur during visually guided emmetropization. MT1–MMP may play an important role by directly remodeling scleral tissue as well as activating MMP–2, and TIMP–3 may play an important role by regulating these MT1–MMP activities.
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