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H. Gao, M. R. Frost, J. T. Siegwart, Jr., T. T. Norton; Patterns of Differential mRNA Expression in Tree Shrew Sclera During Minus-Lens Induced Myopia and Recovery. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1738.
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© ARVO (1962-2015); The Authors (2016-present)
To better understand the emmetropization mechanism, we examined mRNA expression patterns for scleral extracellular matrix (ECM) proteins and signaling molecules during the development of lens induced myopia (LIM) and during recovery from LIM.
Two groups (n=5 each) wore a monocular -5 D lens starting 24 days after normal eye opening (days of VE). The fellow eye served as a control. The LIM group wore the lens for 4 days and developed -2.6 ± 0.4 D of myopia (mean ± SEM). The recovery group wore the lens for 11 days and compensated fully. After 4 days with no lens, the eyes had recovered by 2.0 ± 0.4 D. Normals (n=5) were measured at 24 days of VE. Real-time PCR was used to assess mRNA levels for 18 genes. Correction for multiple comparisons was made with a false discovery rate of 12%.
The pattern during LIM development was consistent with ECM remodeling and matrix loss in the treated eye relative to the control eye. There was a relative decrease in mRNA for TGFβ1 & 2, secreted protein acidic and rich in cysteine (SPARC), thrombospondin 1 (THBS1), and pigment epithelium-derived factor (PEDF). Changes in MT-1 MMP (MMP14) (upregulated) and TIMP3 (downregulated) agree with our previous competitive PCR results. In addition, mRNA for βig-h3 (TGFBI) was upregulated and ADAMTS5 (an aggrecanase) was downregulated. During recovery the pattern was generally reversed. Several mRNAs that differed during LIM returned to normal levels including THBS1, SPARC, TGFBI, PEDF, MMP14, and ADAMTS5. TGFβ1 & 2 and TIMP3 went from downregulation during LIM to upregulation during recovery. TGFβ3 and THBS2 were upregulated in recovery, whereas apolipoprotein E (APOE) was downregulated. Unchanged during LIM or recovery were mRNA levels for apolipoprotein A1 (APOA1), fibronectin (FN1), vimentin (VIM), MMP3, ADAMTS1, and collagen VI (COL6A1).
During LIM development and recovery there is selective scleral ECM remodeling characterized by modulation of mRNA levels for some MMPs, TIMPs, and other proteins that mediate ECM interactions and cell adhesion (SPARC, THBS1, TGFBI). Unlike in chick, APOA1 did not change in tree shrew sclera but APOE was significantly downregulated in recovery. The reductions in THBS1 and PEDF match those seen in our proteomic studies.
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