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Li He, Michael Frost, John Siegwart, Thomas Norton; Bidirectional Gene Expression in Tree Shrew Choroid during Lens-Induced Myopia and Recovery. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3675.
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© ARVO (1962-2015); The Authors (2016-present)
To examine gene expression in the choroid that may communicate retinally-generated GO and STOP signals to the sclera to control axial elongation and refractive error development.
Two groups of tree shrews were used (n=7 per group). GO: lens-induced myopia (LIM): 2 days of monocular −5 D lens wear starting at 24 days of visual experience (DVE); STOP: 2 days of recovery (REC) starting at 35 DVE, after compensation to a −5 D lens. The untreated contralateral eyes served as controls. A total of 77 genes were examined by quantitative real-time PCR (qPCR), including 14 genes that showed bidirectional expression in a whole-transcriptome analysis (RNA-Seq) of 3 animals from each group.
Small refractive changes were observed in the LIM (−1.0 ± 0.2 D; mean ± SEM) and REC groups (+1.3 ± 0.3 D) indicating eyes were early in the process of developing LIM and recovering from LIM. As shown in the figure, 35 of 77 genes showed significant regulation (treated eye - control eye). 13 genes (11 of 14 suggested by RNA-Seq) showed bidirectional regulation. 2 were up-regulated in both. 20 additional genes showed significant differences in either LIM or REC, but not both. Of the 35 genes that showed significant regulation, 18 are involved in signaling pathways including TGFβ/BMP and retinoic acid signaling. The remainder are primarily involved in extracellular matrix remodeling and some may have a role in vascular regulation or angiogenesis. 10 additional genes that showed consistent bidirectional changes in the RNA-Seq analysis, but were not examined with qPCR, would likely also show bidirectional gene expression.
Numerous genes in choroid show bidirectional expression in LIM and REC as assessed with qPCR and even more are suggested on the basis of RNA-Seq. In addition, many genes show altered expression in either LIM or REC but not both. From these results in choroid, it appears that many genes are involved in conveying GO and STOP signals to the sclera. It is highly unlikely that any single gene is primarily responsible for the control of axial elongation and refractive error.
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