Integrated Comparison of GWAS, Transcriptome, and Proteomics Studies Highlights Similarities in the Biological Basis of Animal and Human Myopia

Riddell, Nina

doi:10.1167/iovs.16-20618

Cited by 25 publications

(33 citation statements)

References 69 publications

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“…The TGF-β superfamily of ligands includes BMPs, growth and differentiation factors, anti-müllerian hormone, activin, nodal, and the TGF-β proteins [25]. Signaling begins with the binding of a TGF-β superfamily ligand to a TGF-β type II receptor [26]. The type II receptor is a serine/threonine receptor kinase, which catalyzes the phosphorylation of the type I receptor [25].…”

Section: Discussionmentioning

confidence: 99%

Estrogen repressesTgfbr1andBmpr1aexpression via estrogen receptor beta in MC3T3-E1 cells

Wang

Tang³

et al. 2017

Preprint

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Section: Discussionmentioning

confidence: 99%

Estrogen repressesTgfbr1andBmpr1aexpression via estrogen receptor beta in MC3T3-E1 cells

Wang

Tang³

et al. 2017

Preprint

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“…Moreover, these studies suggested that similar biological processes underlie refractive development in animal models and humans [63].…”

Section: One Of the Leading Causes Of Vision Loss In Several Parts Ofmentioning

confidence: 91%

Analysis of genetic networks regulating refractive eye development in collaborative cross progenitor strain mice reveals new genes and pathways underlying human myopia

Tkatchenko

Shah

Nagasaki

2019

Preprint

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Background: Population studies suggest that genetic factors play an important role in refractive error development; however, the precise role of genetic background and the composition of the signaling pathways underlying refractive eye development remain poorly understood.Methods: Here, we analyzed normal refractive development and susceptibility to formdeprivation myopia in the eight progenitor mouse strains of the Collaborative Cross (CC). We used RNA-seq to analyze gene expression in the retinae of these mice and reconstruct genetic networks and signaling pathways underlying refractive eye development. We also utilized genome-wide gene-based association analysis to identify mouse genes and pathways associated with myopia in humans. Results: Genetic background strongly influenced both baseline refractive development and susceptibility to environmentally-induced myopia. Baseline refractive errors ranged from -21.2 diopters (D) in 129S1/svlmj mice to +22.0 D in CAST/EiJ mice and represented a continuous distribution typical of a quantitative genetic trait. The extent of induced form-deprivation myopia ranged from -5.6 D in NZO/HILtJ mice to -20.0 D in CAST/EiJ mice and also followed a continuous distribution. Whole-genome (RNA-seq) gene expression profiling in retinae from CC progenitor strains identified genes whose expression level correlated with either baseline refractive error or susceptibility to myopia. Expression levels of 2,302 genes correlated with the baseline refractive state of the eye, whereas 1,917 genes correlated with susceptibility to induced myopia. Genome-wide gene-based association analysis in the CREAM and UK Biobank human Page 3 of 47cohorts revealed that 985 of the above genes were associated with myopia in humans, including 847 genes which were implicated in the development of human myopia for the first time.Although the gene sets controlling baseline refractive development and those regulating susceptibility to myopia overlapped, these two processes appeared to be controlled by largely distinct sets of genes. Conclusions: Comparison with data for other animal models of myopia revealed that the genes identified in this study comprise a well-defined set of retinal signaling pathways, which are highly conserved across different vertebrate species. These results identify major signaling pathways involved in refractive eye development and provide attractive targets for the development of anti-myopia drugs. BackgroundMyopia is the most common ocular disorder worldwide [1]. The prevalence of myopia in the U.S. has increased from 25% to ~48% in the last 40 years [2][3][4]. The worldwide prevalence of myopia is predicted to increase from the current 25% to 50% in the next three decades [5], while the prevalence already exceeds 80% in several parts of Asia [6,7]. Myopia often leads to serious blinding complications such as myopic maculopathy, retinal floaters, chorioretinal atrophy, retinoschisis, retinal tears, retinal detachment, and myopic macular degeneration [8][9][10][11][12][13][14][15][16]...

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“…A lot of research has been undertaken to investigate the gene expression patterns that occur during the development of myopia, and a full examination of the genes involved in myopia development is beyond the scope of this review. Analysis has shown that the candidate genes involved in human myopia development display significant overlap with the candidate genes identified in experimental animal models of myopia, indicating these models remain suitable for studying human myopia development (131). It is clear that a large number of genes are upregulated or downregulated during development of or recovery from myopia, some of them in a bidirectional manner.…”

Section: Candidate Genesmentioning

confidence: 99%

Scleral remodelling in myopia and its manipulation: a review of recent advances in scleral strengthening and myopia control

Backhouse¹,

Gentle²

2018

Ann. Eye Sci

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The biological mechanisms of eye growth and refractive development are increasingly well characterised, a result of many careful studies that have been carried out over many years. As the outer coat of the eye, the sclera has the ultimate impact on the restraint or facilitation of eye growth, thus any changes in its biochemistry, ultrastructure, gross morphology and/or biomechanical properties are critical in refractive error development and, in particular, the development of myopia. The current review briefly revisits our basic understanding of the structure and biomechanics of the sclera and how these are regulated and modified during eye growth and myopia development. The review then applies this knowledge in considering recent advances in our understanding of how the mechanisms of scleral remodelling may be manipulated or controlled, in order to constrain eye growth and limit the development of myopia, in particular the higher degrees of myopia that lead to vision loss and blindness. In doing so, the review specifically considers recent approaches to the strengthening of the sclera, through collagen cross-linking, scleral transplantation, implantation or injection of biomaterials, or the direct therapeutic targeting and manipulation of the biochemical mechanisms known to be involved in myopia development. These latest approaches to the control of scleral changes in myopia are, where possible, placed in the context of our understanding of scleral biology, in order to bring a more complete understanding of current and future therapeutic interventions in myopia, and their consequences.

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Integrated Comparison of GWAS, Transcriptome, and Proteomics Studies Highlights Similarities in the Biological Basis of Animal and Human Myopia

Abstract: These findings suggest that genetic and environmental factors control ocular growth via similar biological pathways across species, and support the continued use of animal models for investigating the biological mechanisms underlying human myopia development.

Cited by 25 publications

References 69 publications

Estrogen repressesTgfbr1andBmpr1aexpression via estrogen receptor beta in MC3T3-E1 cells

Estrogen repressesTgfbr1andBmpr1aexpression via estrogen receptor beta in MC3T3-E1 cells

Analysis of genetic networks regulating refractive eye development in collaborative cross progenitor strain mice reveals new genes and pathways underlying human myopia

Scleral remodelling in myopia and its manipulation: a review of recent advances in scleral strengthening and myopia control

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