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Scleral gene expression during recovery from myopia compared with expression during myopia development in tree shrew.

Guo L, Frost MR, Siegwart JT, Norton TT - Mol. Vis. (2014)

Bottom Line: Hyperopic refractive error causes the retina to produce "GO" signals that, through the direct emmetropization pathway, cause scleral remodeling that increases the axial elongation rate of the eye, reducing the hyperopia.In the STAY group, three genes showed significant downregulation.An additional 15 genes showed significant regulation in either GO or STOP conditions but not in both.

View Article: PubMed Central - PubMed

Affiliation: Department of Vision Sciences, School of Optometry, University of Alabama at Birmingham, Birmingham, AL.

ABSTRACT

Purpose: During postnatal refractive development, the sclera receives retinally generated signals that regulate its biochemical properties. Hyperopic refractive error causes the retina to produce "GO" signals that, through the direct emmetropization pathway, cause scleral remodeling that increases the axial elongation rate of the eye, reducing the hyperopia. Myopia causes the retina to generate "STOP" signals that produce scleral remodeling, slowing the axial elongation rate and reducing the myopia. Our aim was to compare the pattern of gene expression produced in the sclera by the STOP signals with the GO gene expression signature we described previously.

Methods: The GO gene expression signature was produced by monocular -5 diopter (D) lens wear for 2 days (ML-2) or 4 days (ML-4); an additional "STAY" condition was examined after eyes had fully compensated for a -5 D lens after 11 days of lens wear (ML-11). After 11 days of -5 D lens wear had produced full refractive compensation, gene expression in the STOP condition was examined during recovery (without the lens) for 2 days (REC-2) or 4 days (REC-4). The untreated contralateral eyes served as a control in all groups. Two age-matched normal groups provided a comparison with the treated groups. Quantitative real-time PCR was used to measure mRNA levels for 55 candidate genes.

Results: The STAY group compensated fully for the lens (treated eye versus control eye, -5.1±0.2 D). Wearing the lens, the hyperopic signal for elongation had dissipated (-0.3±0.3 D). In the STOP groups, the refraction in the recovering eyes became less myopic relative to the control eyes (REC-2, +1.3±0.3 D; REC-4, +2.6±0.4 D). In the STAY group, three genes showed significant downregulation. However, many genes that were significantly altered in GO showed smaller, nonsignificant, expression differences in the same direction in STAY, suggesting the gene expression signature in STAY is a greatly weakened form of the GO signature. In the STOP groups, a different gene expression pattern was observed, characterized by mostly upregulation with larger fold differences after 4 days than after 2 days of recovery. Eleven of the 55 genes examined showed significant bidirectional GO/STOP regulation in the ML-2 and REC-2 groups, and 13 genes showed bidirectional regulation in the ML-4 and REC-4 groups. Eight of these genes (NPR3, CAPNS1, NGEF, TGFB1, CTGF, NOV, TIMP1, and HS6ST1) were bidirectionally regulated at both time points in the GO and STOP conditions. An additional 15 genes showed significant regulation in either GO or STOP conditions but not in both.

Conclusions: Many genes are involved in scleral remodeling and the control of axial length. The STOP (recovery) gene expression signature in the sclera involves some of the same genes, bidirectionally regulated, as the GO signature. However, other genes, regulated in GO, are not differentially regulated in STOP, and others show differential regulation only in STOP.

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Gene expression differences. Comparison of gene expression differences (treated eye versus control eye) produced by (A) 2 days of minus-lens wear, (B) 4 days of minus-lens wear, (C) 11 days of minus-lens wear, (D) 2 days of recovery from 11 days of minus-lens wear, and (E) 4 days of recovery from 11 days of minus-lens wear. Bar color is arbitrary and intended to help in comparing the same gene in the five different conditions. Error bars=SEM. The data in panels (A) and (B) are reproduced with permission from [45] and are presented here for comparison.
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f5: Gene expression differences. Comparison of gene expression differences (treated eye versus control eye) produced by (A) 2 days of minus-lens wear, (B) 4 days of minus-lens wear, (C) 11 days of minus-lens wear, (D) 2 days of recovery from 11 days of minus-lens wear, and (E) 4 days of recovery from 11 days of minus-lens wear. Bar color is arbitrary and intended to help in comparing the same gene in the five different conditions. Error bars=SEM. The data in panels (A) and (B) are reproduced with permission from [45] and are presented here for comparison.

Mentions: The fold differences in gene expression between the treated and control eyes in the GO groups (ML-2 and ML-4) are shown in Figure 5A,B; expression values are also listed in Figure 4. The variability in expression across animals within each group was low, as evidenced by the small SEM values. The GO patterns were reported previously as part of a larger study [45] and are presented here to allow comparison with the STAY and STOP expression patterns. Most but not all of the sampled genes were downregulated in the treated eyes relative to the control eyes.


Scleral gene expression during recovery from myopia compared with expression during myopia development in tree shrew.

Guo L, Frost MR, Siegwart JT, Norton TT - Mol. Vis. (2014)

Gene expression differences. Comparison of gene expression differences (treated eye versus control eye) produced by (A) 2 days of minus-lens wear, (B) 4 days of minus-lens wear, (C) 11 days of minus-lens wear, (D) 2 days of recovery from 11 days of minus-lens wear, and (E) 4 days of recovery from 11 days of minus-lens wear. Bar color is arbitrary and intended to help in comparing the same gene in the five different conditions. Error bars=SEM. The data in panels (A) and (B) are reproduced with permission from [45] and are presented here for comparison.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4265769&req=5

f5: Gene expression differences. Comparison of gene expression differences (treated eye versus control eye) produced by (A) 2 days of minus-lens wear, (B) 4 days of minus-lens wear, (C) 11 days of minus-lens wear, (D) 2 days of recovery from 11 days of minus-lens wear, and (E) 4 days of recovery from 11 days of minus-lens wear. Bar color is arbitrary and intended to help in comparing the same gene in the five different conditions. Error bars=SEM. The data in panels (A) and (B) are reproduced with permission from [45] and are presented here for comparison.
Mentions: The fold differences in gene expression between the treated and control eyes in the GO groups (ML-2 and ML-4) are shown in Figure 5A,B; expression values are also listed in Figure 4. The variability in expression across animals within each group was low, as evidenced by the small SEM values. The GO patterns were reported previously as part of a larger study [45] and are presented here to allow comparison with the STAY and STOP expression patterns. Most but not all of the sampled genes were downregulated in the treated eyes relative to the control eyes.

Bottom Line: Hyperopic refractive error causes the retina to produce "GO" signals that, through the direct emmetropization pathway, cause scleral remodeling that increases the axial elongation rate of the eye, reducing the hyperopia.In the STAY group, three genes showed significant downregulation.An additional 15 genes showed significant regulation in either GO or STOP conditions but not in both.

View Article: PubMed Central - PubMed

Affiliation: Department of Vision Sciences, School of Optometry, University of Alabama at Birmingham, Birmingham, AL.

ABSTRACT

Purpose: During postnatal refractive development, the sclera receives retinally generated signals that regulate its biochemical properties. Hyperopic refractive error causes the retina to produce "GO" signals that, through the direct emmetropization pathway, cause scleral remodeling that increases the axial elongation rate of the eye, reducing the hyperopia. Myopia causes the retina to generate "STOP" signals that produce scleral remodeling, slowing the axial elongation rate and reducing the myopia. Our aim was to compare the pattern of gene expression produced in the sclera by the STOP signals with the GO gene expression signature we described previously.

Methods: The GO gene expression signature was produced by monocular -5 diopter (D) lens wear for 2 days (ML-2) or 4 days (ML-4); an additional "STAY" condition was examined after eyes had fully compensated for a -5 D lens after 11 days of lens wear (ML-11). After 11 days of -5 D lens wear had produced full refractive compensation, gene expression in the STOP condition was examined during recovery (without the lens) for 2 days (REC-2) or 4 days (REC-4). The untreated contralateral eyes served as a control in all groups. Two age-matched normal groups provided a comparison with the treated groups. Quantitative real-time PCR was used to measure mRNA levels for 55 candidate genes.

Results: The STAY group compensated fully for the lens (treated eye versus control eye, -5.1±0.2 D). Wearing the lens, the hyperopic signal for elongation had dissipated (-0.3±0.3 D). In the STOP groups, the refraction in the recovering eyes became less myopic relative to the control eyes (REC-2, +1.3±0.3 D; REC-4, +2.6±0.4 D). In the STAY group, three genes showed significant downregulation. However, many genes that were significantly altered in GO showed smaller, nonsignificant, expression differences in the same direction in STAY, suggesting the gene expression signature in STAY is a greatly weakened form of the GO signature. In the STOP groups, a different gene expression pattern was observed, characterized by mostly upregulation with larger fold differences after 4 days than after 2 days of recovery. Eleven of the 55 genes examined showed significant bidirectional GO/STOP regulation in the ML-2 and REC-2 groups, and 13 genes showed bidirectional regulation in the ML-4 and REC-4 groups. Eight of these genes (NPR3, CAPNS1, NGEF, TGFB1, CTGF, NOV, TIMP1, and HS6ST1) were bidirectionally regulated at both time points in the GO and STOP conditions. An additional 15 genes showed significant regulation in either GO or STOP conditions but not in both.

Conclusions: Many genes are involved in scleral remodeling and the control of axial length. The STOP (recovery) gene expression signature in the sclera involves some of the same genes, bidirectionally regulated, as the GO signature. However, other genes, regulated in GO, are not differentially regulated in STOP, and others show differential regulation only in STOP.

Show MeSH
Related in: MedlinePlus