Alterations in Protein Expression in Tree Shrew Sclera during Development of Lens-Induced Myopia and Recovery

Frost, Michael R.; Norton, Thomas T.

doi:10.1167/iovs.11-8354

Cited by 62 publications

(59 citation statements)

References 55 publications

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“…It must be acknowledged that a ''yoking effect,'' between treated and contralateral control eyes, has been reported in other studies. 9 However, we compared the contralateral control eye data (refraction, vitreous chamber depth, and axial length) of the vehicle and the TIMP-2 groups and found no significant difference, suggesting that, in the current study, TIMP-2 treatment had no yoking effect in the control eyes. Based on previously published studies, 18 the dose of TIMP-2 delivered subconjunctivally was estimated to result in a concentration of approximately 70 nM in the 7-mm button of tree shrew sclera, which is approximately 3.5 to 7 times the IC 50 value of MMP-2 activation.…”

contrasting

confidence: 55%

Reduced Scleral TIMP-2 Expression Is Associated With Myopia Development: TIMP-2 Supplementation Stabilizes Scleral Biomarkers of Myopia and Limits Myopia Development

Liu

Kenning

Jobling

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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contrasting

confidence: 55%

Reduced Scleral TIMP-2 Expression Is Associated With Myopia Development: TIMP-2 Supplementation Stabilizes Scleral Biomarkers of Myopia and Limits Myopia Development

Liu

Kenning

Jobling

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…After 2 days of LIM, scleral gene expression is altered; a scleral GO signature is found (Guo et al, 2013) and creep rate is elevated (Siegwart, Jr. & Norton, 1999). Very similar, somewhat stronger gene expression changes are found after four days of LIM (Frost & Norton, 2012; Guo et al, 2013) and scleral creep rate reaches a peak at this time (Siegwart, Jr. & Norton, 1999). After 11 days of LIM, the eyes have fully compensated for the minus lens but scleral viscoelasticity remains slightly elevated (Siegwart, Jr. & Norton, 1999) and some gene expression differences remain in the sclera (Guo, personal communication, 2013) suggesting the presence of STAY signals in the choroid at this time point.…”

Section: Introductionmentioning

confidence: 58%

“…Previous studies of mRNA and protein levels in tree shrew sclera have found alterations in expression levels not only in the treated eyes, but also in the untreated fellow control eyes when compared with age-matched normal eyes (Frost & Norton, 2012; Gao et al., 2011). Because (unpaired) comparisons of expression between groups of animals are less sensitive than (paired) comparisons between the two eyes within an animal, fewer significant differences are typically detected.…”

Section: Resultsmentioning

confidence: 97%

Gene expression signatures in tree shrew choroid during lens-induced myopia and recovery

Frost

Siegwart

et al. 2014

Experimental Eye Research

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Gene expression in tree shrew choroid was examined during the development of minus-lens induced myopia (LIM, a GO condition), after completion of minus-lens compensation (a STAY condition), and early in recovery (REC) from induced myopia (a STOP condition). Five groups of tree shrews (n = 7 per group) were used. Starting 24 days after normal eye-opening (days of visual experience [DVE]), one minus-lens group wore a monocular −5 D lens for 2 days (LIM-2), another minus-lens group achieved stable lens compensation while wearing a monocular −5 D lens for 11 days (LIM-11); a recovery group also wore a −5D lens for 11 days and then received 2 days of recovery starting at 35 DVE (REC-2). Two age-matched normal groups were examined at 26 DVE and 37 DVE. Quantitative PCR was used to measure the relative differences in mRNA levels in the choroid for 77 candidate genes that were selected based on previous studies or because a whole-transcriptome analysis suggested their expression would change during myopia development or recovery. Small myopic changes were observed in the treated eyes of the LIM-2 group (−1.0 ± 0.2 D; mean ± SEM) indicating eyes were early in the process of developing LIM. The LIM-11 group exhibited complete refractive compensation (−5.1 ± 0.2 D) that was stable for five days. The REC-2 group recovered by 1.3 ± 0.3 D from full refractive compensation. Sixty genes showed significant mRNA expression differences during normal development, LIM, or REC conditions. In LIM-2 choroid (GO), 18 genes were significantly down-regulated in the treated eyes relative to the fellow control eyes and 10 genes were significantly up-regulated. In LIM-11 choroid (STAY), 10 genes were significantly down-regulated and 12 genes were significantly up-regulated. Expression patterns in GO and STAY were similar, but not identical. All genes that showed differential expression in GO and STAY were regulated in the same direction in both conditions. In REC-2 choroid (STOP), 4 genes were significantly down-regulated and 18 genes were significantly up-regulated. Thirteen genes showed bi-directional regulation in GO vs. STOP. The pattern of differential gene expression in STOP was very different from that in GO or in STAY. Significant regulation was observed in genes involved in signaling as well as extracellular matrix turnover. These data support an active role for the choroid in the signaling cascade from retina to sclera. Distinctly different treated eye vs. control eye mRNA signatures are present in the choroid in the GO, STAY, and STOP conditions. The STAY signature, present after full compensation has occurred and the GO visual stimulus is no longer present, may participate in maintaining an elongated globe. The 13 genes with bi-directional expression differences in GO and STOP responded in a sign of defocus-dependent manner. Taken together, these data further suggest that a network of choroidal gene expression changes generate the signal that alters scleral fibroblast gene expression and axial elongation rate.

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“…In contrast, tree shrews at similar ages that recover from an induced myopia begin recovery with elongated eyes and scleras that have altered protein levels, mRNA levels and biomechanical properties. (Siegwart and Norton 1999, Frost and Norton 2012, Guo, Frost et al 2012, Guo, Frost et al 2013, Grytz and Siegwart 2015). The effectiveness of the red light in slowing axial elongation in eyes with normal scleras suggests that elongated eyes (an “eye-size” factor) does not explain the difference between the lack of response to plus lens wear and the recovery response when a minus lens is removed after compensation has occurred.…”

Section: 0 Discussionmentioning

confidence: 99%

“…Siegwart and Norton (2010) suggested that, in a normal-size eye, the emmetropization mechanism may not be able to slow axial elongation below a genetically pre-programmed minimum amount. In contrast, in an eye that has been elongated after minus lens wear, the sclera has undergone remodeling of the extracellular matrix and has altered protein and mRNA levels (Siegwart and Norton 1999, Frost, Guo et al 2012, Guo, Frost et al 2013, Grytz and Siegwart 2015). The altered sclera may respond to the signals from the emmetropization mechanism although normal sclera cannot.…”

Section: Introductionmentioning

confidence: 99%

Long-wavelength (red) light produces hyperopia in juvenile and adolescent tree shrews

2017

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In infant tree shrews, exposure to narrow-band long-wavelength (red) light, that stimulates long-wavelength sensitive cones almost exclusively, slows axial elongation and produces hyperopia. We asked if red light produces hyperopia in juvenile and adolescent animals, ages when plus lenses are ineffective. Animals were raised in fluorescent colony lighting (100–300 lux) until they began 13 days of red-light treatment at 11 (n=5, “infant”), 35 (n=5, “juvenile”) or 95 (n=5, “adolescent”) days of visual experience (DVE). LEDs provided 527–749 lux on the cage floor. To control for the higher red illuminance, a fluorescent control group (n=5) of juvenile (35 DVE) animals was exposed to ~ 975 lux. Refractions were measured daily; ocular component dimensions at the start and end of treatment and end of recovery in colony lighting. These groups were compared with normals (n=7). In red light, the refractive state of both juvenile and adolescent animals became significantly (P<0.05) hyperopic: juvenile 3.9±1.0 diopters (D, mean±SEM) vs. normal 0.8±0.1 D; adolescent 1.6±0.2 D vs. normal 0.4±0.1 D. The fluorescent control group refractions (0.6±0.3 D) were normal. In red-treated juveniles the vitreous chamber was significantly smaller than normal (P<0.05): juvenile 2.67±0.03 mm vs. normal 2.75±0.02 mm. The choroid was also significantly thicker: juvenile 77±4 μm vs. normal 57±3 μm (P<0.05). Although plus lenses do not restrain eye growth in juvenile tree shrews, the red light-induced slowed growth and hyperopia in juvenile and adolescent tree shrews demonstrates that the emmetropization mechanism is still capable of restraining eye growth at these ages.

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Alterations in Protein Expression in Tree Shrew Sclera during Development of Lens-Induced Myopia and Recovery

Cited by 62 publications

References 55 publications

Reduced Scleral TIMP-2 Expression Is Associated With Myopia Development: TIMP-2 Supplementation Stabilizes Scleral Biomarkers of Myopia and Limits Myopia Development

Reduced Scleral TIMP-2 Expression Is Associated With Myopia Development: TIMP-2 Supplementation Stabilizes Scleral Biomarkers of Myopia and Limits Myopia Development

Gene expression signatures in tree shrew choroid during lens-induced myopia and recovery

Long-wavelength (red) light produces hyperopia in juvenile and adolescent tree shrews

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