<i>Egr-1</i>mRNA Expression Is a Marker for the Direction of Mammalian Ocular Growth

Ashby, Regan; Zeng, Guang; Leotta, Amelia J.; Tse, Dennis Y.; McFadden, Sally A

doi:10.1167/iovs.13-11708

Cited by 36 publications

(41 citation statements)

References 51 publications

(84 reference statements)

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“…2a, b). The previously reported myopia-related genes (Ashby et al, 2014, Hawthorne and Young, 2013, Ma et al, 2014, Mathis et al, 2014, McGlinn et al, 2007, Ritchey et al, 2012, Wisard et al, 2011, Yoshikawa et al, 2014) such as Bmp2, Ednrb, Fgf2, Igf1, Il18, Irbp, Lumican, Sfrp1, Tgfb1, Vegfa, Vip, and Wnt2b were not found in the PC1 group in vivo , which indicates that they responded less to violet light. In the PC1 group, only one myopia protective gene (Pardue et al, 2013), EGR1 (ZENK, zif268), was found among the previously reported myopia related genes (Fig.…”

Section: Resultsmentioning

confidence: 74%

“…EGR1 was first found to be involved in the suppression of elongation in the chick eye (Fischer et al, 1999), and the eye elongated when EGR1 was knocked down in mouse (Schippert et al, 2007), suggesting this gene is one of the most important genes related to myopia progression. Ashby et al (2014) reported that Egr-1 mRNA levels were elevated to almost 2x the control after 3 days recovering from −5 D lens removal in a guinea pig model. In the current study, EGR1 mRNA levels in VL+ group were elevated to almost 2x the VL– group in both control and covered eyes (Fig.…”

Section: Discussionmentioning

confidence: 97%

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Violet Light Exposure Can Be a Preventive Strategy Against Myopia Progression

et al. 2017

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Prevalence of myopia is increasing worldwide. Outdoor activity is one of the most important environmental factors for myopia control. Here we show that violet light (VL, 360–400 nm wavelength) suppresses myopia progression. First, we confirmed that VL suppressed the axial length (AL) elongation in the chick myopia model. Expression microarray analyses revealed that myopia suppressive gene EGR1 was upregulated by VL exposure. VL exposure induced significantly higher upregulation of EGR1 in chick chorioretinal tissues than blue light under the same conditions. Next, we conducted clinical research retrospectively to compare the AL elongation among myopic children who wore eyeglasses (VL blocked) and two types of contact lenses (partially VL blocked and VL transmitting). The data showed the VL transmitting contact lenses suppressed myopia progression most. These results suggest that VL is one of the important outdoor environmental factors for myopia control. Since VL is apt to be excluded from our modern society due to the excessive UV protection, VL exposure can be a preventive strategy against myopia progression.

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Section: Resultsmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 97%

Violet Light Exposure Can Be a Preventive Strategy Against Myopia Progression

et al. 2017

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“…Further evidence of the protective effects of bright light have been shown in a number of experiments with animal models. Using chickens (Ashby et al, 2009; Ashby and Schaeffel, 2010; Ashby et al, 2014; Backhouse et al, 2013; Lan et al, 2014), primates (Smith et al, 2012), and tree shrews (Norton and Siegwart, 2013), bright light has been reported to decrease the myopic shift induced by FD or lens defocus (Ashby and Schaeffel, 2010). These protective effects have been attributed to increased retinal DA levels and DA receptor activation as the DA D 2 -like receptor antagonist, spiperone blocks the protective effects of bright light (Ashby and Schaeffel, 2010).…”

Section: Effects Of Altered Da Levels On Myopic Eye Growthmentioning

confidence: 99%

Dopamine signaling and myopia development: What are the key challenges

Zhou

Pardue

Iuvone

et al. 2017

Progress in Retinal and Eye Research

230

203

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In the face of an “epidemic” increase in myopia over the last decades and myopia prevalence predicted to reach 2.5 billion people by the end of this decade, there is an urgent need to develop effective and safe therapeutic interventions to slow down this “myopia booming” and prevent myopia-related complications and vision loss. Dopamine (DA) is an important neurotransmitter in the retina and mediates diverse functions including development, visual signaling, and refractive development. Inspired by the convergence of epidemiological and animal studies in support of the inverse relationship between outdoor activity and risk of developing myopia and by the close biological relationship between light exposure and dopamine release/signaling, we felt it is timely and important to critically review the role of DA in myopia development. This review will revisit several key points of evidence for and against DA mediating light control of myopia: 1) the causal role of extracellular retinal DA levels, 2) the mechanism and action of dopamine D1 and D2 receptors and 3) the roles of cellular/circuit retinal pathways. We examine the experiments that show causation by altering DA, DA receptors and visual pathways using pharmacological, transgenic, or visual environment approaches. Furthermore, we critically evaluate the safety issues of a DA-based treatment strategy and some approaches to address these issues. The review identifies the key questions and challenges in translating basic knowledge on DA signaling and myopia from animal studies into effective pharmacological treatments for myopia in children.

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“…We chose EGR1 as a candidate gene for association analysis of myopia, based on its functionality evidence: (1) Animal model studies of induced myopia and gene knock-out have all demonstrated the important role of EGR1 in myopia (Schippert et al, 2007); (2) EGR1 is a critical protein for eye growth and myopisation (Fischer et al, 1999;Ashby et al, 2014). The SNP rs11743810 selected here is itself the tSNP covering the EGR1 gene region's LD plot with an r 2 of 1.000 00 and an estimated power for association test of 0.997 83 (Table 4), suggesting the high efficiency of the association analysis.…”

Section: Egr1 Gene Resultsmentioning

confidence: 99%

“…Fischer et al (1999) also found a significant association of the EGR1 expression level in the retina with eyeball growth in the animal model. Moreover, a recent myopia animal study indicated that EGR1 might play a role in signaling eye growth bidirectionally (Ashby et al, 2014). However, Li et al (2008) screened mutations in the EGR1 gene region in a small group of unrelated high myopia individuals (n=96), but found no causal variations in their work.…”

mentioning

confidence: 99%

Controversial opinion: evaluation of EGR1 and LAMA2 loci for high myopia in Chinese populations

Lin

Huang

Lü

et al. 2016

J. Zhejiang Univ. Sci. B

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Abstract:Functional studies have suggested the important role of early growth response 1 (EGR1) and Laminin α2-chain (LAMA2) in human eye development. Genetic studies have reported a significant association of the single nucleotide polymorphism (SNP) in the LAMA2 gene with myopia. This study aimed to evaluate the association of the tagging SNPs (tSNPs) in the EGR1 and LAMA2 genes with high myopia in two independent Han Chinese populations. Four tSNPs (rs11743810 in the EGR1 gene; rs2571575, rs9321170, and rs1889891 in the LAMA2 gene) were selected, according to the HapMap database (http://hapmap.ncbi.nlm.nih.gov), and were genotyped using the ligase detection reaction (LDR) approach for 167 Han Chinese nuclear families with extremely highly myopic offspring (<−10.0 diopters) and an independent group with 485 extremely highly myopic cases (<−10.0 diopters) and 499 controls. Direct sequencing was used to confirm the LDR results in twenty randomly selected subjects. Family-based association analysis was performed using the family-based association test (FBAT) software package (Version 1.5.5). Population-based association analysis was performed using the Chi-square test. The association analysis power was estimated using online software (http://design.cs.ucla.edu). The FBAT demonstrated that all four tSNPs tested did not show association with high myopia (P>0.05). Haplotype analysis of tSNPs in the LAMA2 genes also did not show a significant association (P>0.05). Meanwhile, population-based association analysis also showed no significant association results with high myopia (P>0.05). On the basis of our family-and population-based analyses for the Han Chinese population, we did not find positive association signals of the four SNPs in the LAMA2 and EGR1 genes with high myopia.

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Egr-1mRNA Expression Is a Marker for the Direction of Mammalian Ocular Growth

Abstract: Egr-1 mRNA levels in a mammalian retina show a bi-directional persistent response to opposing ocular growth stimuli. This suggests retinal Egr-1 might act as a signal for the direction of ocular growth in different species.

Cited by 36 publications

References 51 publications

Violet Light Exposure Can Be a Preventive Strategy Against Myopia Progression

Violet Light Exposure Can Be a Preventive Strategy Against Myopia Progression

Dopamine signaling and myopia development: What are the key challenges

Controversial opinion: evaluation of EGR1 and LAMA2 loci for high myopia in Chinese populations

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