Bidirectional, Optical Sign-Dependent Regulation of BMP2 Gene Expression in Chick Retinal Pigment Epithelium

Zhang, Yan; Liu, Yue; Wildsoet, Christine F.

doi:10.1167/iovs.12-9917

Cited by 50 publications

(88 citation statements)

References 47 publications

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“…This testing strategy reduces the influence of inter-animal variability, but leaves open the question of whether the behavior of the fellow eyes was normal. Although some studies using this chick model for myopia have reported interocular (yoking) interactions (Zhang, Liu, & Wildsoet, 2012), a previous study involving mechanical testing of strips of chick sclera observed no statistical difference between contralateral controls and eyes from untreated, normal chicks (Phillips et al, 2000). …”

Section: Discussionmentioning

confidence: 85%

Intact globe inflation testing of changes in scleral mechanics in myopia and recovery

Lewis

Garcia²,

Rani³

et al. 2014

Experimental Eye Research

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The purpose of this study was to examine the effects of myopia-inducing and myopia recovery conditions on the scleral biomechanics of enucleated eyes of young chicks. Enucleated eyes from 5-day old chicks, with fiducial markers attached at 5 locations on the external sclera, were placed in a custom-built chamber filled with phosphate-buffered saline, and subjected to controlled increments in intraocular pressure (IOP). IOP was initially ramped from 15 to 100 mmHg and then maintained at 100 mmHg for one hour, with eyes photographed at a rate of 0.1 Hz over the same period. There were two experimental groups, one in which chicks were monocularly form deprived for four days to induce myopia, and the other in which chicks were allowed two days of recovery from myopia induced by two days of form deprivation. For all chicks, the contralateral (fellow) eyes served as controls. Myopic eyes showed less initial deformation relative to their fellows, while no difference was recorded between recovering eyes and their fellows over the same time frame. With exposure to sustained elevated pressure, eyes in all groups displayed time-dependent changes in creep behavior, which included a linear region of secondary, steady creep. The creep deformation of myopic eyes was significantly higher than that of their fellows, consistent with results of previous studies using uniaxial loading of scleral strips. When allowed only 2 days to recover from induced myopia, previously myopic eyes continued to show increased creep deformation. Compared to results reported in studies involving scleral strips, our whole globe testing yielded higher values for creep rate. Whole globe inflation testing provides a viable, less anatomically disruptive and readily adaptable method for investigating scleral biomechanics than uniaxial tensile strip testing. Furthermore, our results suggest that elastic stretching does not contribute to the increased axial elongation underlying myopia in young chick eyes. They also confirm the very limited involvement of the sclera in the early recovery from myopia, reflecting the well documented lag in scleral versus choroidal recovery responses.

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Section: Discussionmentioning

confidence: 85%

Intact globe inflation testing of changes in scleral mechanics in myopia and recovery

Lewis

Garcia²,

Rani³

et al. 2014

Experimental Eye Research

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“…33 Finally, recent studies have demonstrated differential expression of a number of genes in the RPE of eyes undergoing experimental manipulations perturbing normal eye growth. 34,35 …”

Section: The Role Of the Rpe In Eye Growth Regulationmentioning

confidence: 99%

RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia

Zhang¹,

Wildsoet²

2015

Progress in Molecular Biology and Translational Science

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Myopia is the most common type of refractive errors and one of the world’s leading causes of blindness. Visual manipulations in animal models have provided convincing evidence for the role of environmental factors in myopia development. These models along with in vitro studies have provided important insights into underlying mechanisms. The key locations of the retinal pigment epithelium (RPE) and choroid make them plausible conduits for relaying growth regulatory signals originating in the retina to the sclera, which ultimately determines eye size and shape. Identifying the key signal molecules and their targets may lead to the development of new myopia control treatments. This section summarizes findings implicating the RPE and choroid in myopia development. For RPE and/or choroid, changes in morphology, activity of ion channels/transporters, as well as in gene and protein expression, have been linked to altered eye growth. Both tissues thus represent potential targets for novel therapies for myopia.

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“…Although changes in levels of proteins or other molecules presumably are key to actually transmitting signals from choroid to sclera, it has been found that changes in mRNA levels can identify the responses of the cells in tissues and are useful in identifying pathways of interest (Gao et al, 2011, 2013; Schippert et al, 2006; Shelton et al, 2008; Siegwart & Norton, 2005; Stone et al, 2011; Zhang, Liu, & Wildsoet, 2012). In a previous paper in tree shrew choroid (He et al, 2014), we examined the gene expression signatures produced by ML wear (GO) and by recovery from induced myopia (a STOP condition).…”

Section: Introductionmentioning

confidence: 99%

Gene expression signatures in tree shrew choroid in response to three myopiagenic conditions

Frost

Siegwart

et al. 2014

Vision Research

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We examined gene expression in tree shrew choroid in response to three different myopiagenic conditions: minus lens (ML) wear, form deprivation (FD), and continuous darkness (DK). Four groups of tree shrews (n = 7 per group) were used. Starting 24 days after normal eye opening (days of visual experience [DVE]), the ML group wore a monocular −5 D lens for 2 days. The FD group wore a monocular translucent diffuser for 2 days. The DK group experienced continuous darkness binocularly for 11 days, starting at 17 DVE. An age-matched normal group was examined at 26 DVE. Quantitative PCR was used to measure the relative (treated eye vs. control eye) differences in mRNA levels in the choroid for 77 candidate genes. Small myopic changes were observed in the treated eyes (relative to the control eyes) of the ML group (−1.0 ± 0.2 D; mean ± SEM) and FD group (−1.9 ± 0.2 D). A larger myopia developed in the DK group (−4.4 ± 1.0 D) relative to Normal eyes (both groups, mean of right and left eyes). In the ML group, 28 genes showed significant differential mRNA expression; eighteen were down-regulated. A very similar pattern occurred in the FD group; twenty-seven of the same genes were similarly regulated, along with five additional genes. Fewer expression differences in the DK group were significant compared to normal or the control eyes of the ML and FD groups, but the pattern was similar to that of the ML and FD differential expression patterns. These data suggest that, at the level of the choroid, the gene expression signatures produced by “GO” emmetropization signals are highly similar despite the different visual conditions.

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Bidirectional, Optical Sign-Dependent Regulation of BMP2 Gene Expression in Chick Retinal Pigment Epithelium

Abstract: That mRNA expression of BMP2 in chick RPE shows bidirectional, defocus sign-dependent changes is suggestive of a role for BMP2 in eye growth regulation, although the diffuse ocular expression of BMP2 and its receptors suggests complex growth-modulatory signal pathways.

Cited by 50 publications

References 47 publications

Intact globe inflation testing of changes in scleral mechanics in myopia and recovery

Intact globe inflation testing of changes in scleral mechanics in myopia and recovery

RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia

Gene expression signatures in tree shrew choroid in response to three myopiagenic conditions

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