Alterations of Glutamate and γ-Aminobutyric Acid Expressions in Normal and Myopic Eye Development in Guinea Pigs

Li, Guoping; Xiang, Yang; Wu, Jianfeng; Huang, Jie; Jiang, Wenjun; Guo, Dadong; Bi, Hongsheng

doi:10.1167/iovs.16-21130

Cited by 21 publications

(15 citation statements)

References 62 publications

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“…These predictions have been widely confirmed and confirmed in previous experiments. For example, studies by Guoping et al confirmed that cyclic adenosine monophosphate activates retinal apolipoprotein A1 expression and inhibits myopia growth [ 49 ]. Ikuno et al's study showed that glutamic acid can regulate excitatory neurotransmitters in the retina and thus play a pivotal role in eye development and lens-induced myopia (LIM) [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Multifactor-Driven Myopia Disease Modules to Guide Personalized Treatment and Drug Development

Liu

2022

Computational and Mathematical Methods in Medicine

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Myopia is recognized as a multifactor, multicascade complex disease. However, people still know little about the pathogenesis of myopia. Therefore, we aim to guide the personalized treatment, drug research, and development of myopia. Here, based on the interaction network of myopia-related genes, this study constructed a multifactor-driven myopia disease module map. We first identified differentially expressed (DE) miRNAs in myopia. Then, we constructed a myopia-related protein interaction network targeted by these DE miRNAs. Further, we clustered the network into modules and identified module-driven factors, including ncRNAs and transcription factors. Especially, miR-16-5p and miR-34b-5p significantly differentially expressed drive the pathogenic module to influence the progression of myopia. At the same time, transcription factors were involved in myopia-related functions and pathways by regulating the expression of genes in modules, such as Ctnnb1, Myc, and Notch1. In addition, we identified 43 genes in modules that played key roles in the development and progression of myopia such as Vamp2, Egfr, and Wasl. Finally, we constructed a comprehensive multifactor-driven myopia pathogenic module landscape and predicted potential drug and drug targets for myopia. In general, our work not only provided candidates for biological experiments which laid the foundation for the in-depth study of myopia but also has a high reference value for the personalized treatment of myopia and drug development.

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Section: Discussionmentioning

confidence: 99%

Analysis of Multifactor-Driven Myopia Disease Modules to Guide Personalized Treatment and Drug Development

Liu

2022

Computational and Mathematical Methods in Medicine

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“…Some previous studies have reported down-regulation of GABA-related genes or retinal GABA content during lens and occlusion myopia induction [ 51 , 58 , 105 , 106 ], however, most reports are consistent with the increase in GABA pathway signalling suggested here. Specifically, the present findings are in agreement with previous reports of up-regulation of the NSF protein during lens-induced myopia in mouse [ 63 ], and up-regulation of the GABA A receptor mRNA and protein [ 107 ] and increased retinal GABA content during lens-induced myopia in guinea pigs [ 107 , 108 ]. This pattern of expression responses is also consistent with drug studies showing that GABA receptor antagonists inhibit myopia development [ 105 , 109 , 110 ].…”

Section: Discussionsupporting

confidence: 93%

Short term optical defocus perturbs normal developmental shifts in retina/RPE protein abundance

Riddell

Faou

2018

BMC Dev Biol

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BackgroundMyopia (short-sightedness) affects approximately 1.4 billion people worldwide, and prevalence is increasing. Animal models induced by defocusing lenses show striking similarity with human myopia in terms of morphology and the implicated genetic pathways. Less is known about proteome changes in animals. Thus, the present study aimed to improve understanding of protein pathway responses to lens defocus, with an emphasis on relating expression changes to no lens control development and identifying bidirectional and/or distinct pathways across myopia and hyperopia (long-sightedness) models.ResultsQuantitative label-free proteomics and gene set enrichment analysis (GSEA) were used to examine protein pathway expression in the retina/RPE of chicks following 6 h and 48 h of myopia induction with − 10 dioptre (D) lenses, hyperopia induction with +10D lenses, or normal no lens rearing. Seventy-one pathways linked to cell development and neuronal maturation were differentially enriched between 6 and 48 h in no lens chicks. The majority of these normal developmental changes were disrupted by lens-wear (47 of 71 pathways), however, only 11 pathways displayed distinct expression profiles across the lens conditions. Most notably, negative lens-wear induced up-regulation of proteins involved in ATP-driven ion transport, calcium homeostasis, and GABA signalling between 6 and 48 h, while the same proteins were down-regulated over time in normally developing chicks. Glutamate and bicarbonate/chloride transporters were also down-regulated over time in normally developing chicks, and positive lens-wear inhibited this down-regulation.ConclusionsThe chick retina/RPE proteome undergoes extensive pathway expression shifts during normal development. Most of these pathways are further disrupted by lens-wear. The identified expression patterns suggest close interactions between neurotransmission (as exemplified by increased GABA receptor and synaptic protein expression), cellular ion homeostasis, and associated energy resources during myopia induction. We have also provided novel evidence for changes to SLC-mediated transmembrane transport during hyperopia induction, with potential implications for signalling at the photoreceptor-bipolar synapse. These findings reflect a key role for perturbed neurotransmission and ionic homeostasis in optically-induced refractive errors, and are predicted by our Retinal Ion Driven Efflux (RIDE) model.Electronic supplementary materialThe online version of this article (10.1186/s12861-018-0177-1) contains supplementary material, which is available to authorized users.

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“…Guoping et al . reported that the ratio of glutamate to GABA was upregulated in myopic guinea pig eyes, suggesting that the ratio of excitatory and inhibitory neurotransmitters may be important for myopic eye growth. Several studies in animals and humans implicate defects in glutamate receptors with myopia .…”

Section: Ocular Diurnal Rhythms and Eye Growthmentioning

confidence: 99%

Circadian rhythms, refractive development, and myopia

Chakraborty

Ostrin

Nickla

et al. 2018

Ophthalmic Physiologic Optic

166

145

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Purpose Despite extensive research, mechanisms regulating postnatal eye growth and those responsible for ametropias are poorly understood. With the marked recent increases in myopia prevalence, robust and biologically-based clinical therapies to normalize refractive development in childhood are needed. Here, we review classic and contemporary literature about how circadian biology might provide clues to develop a framework to improve the understanding of myopia etiology, and possibly lead to rational approaches to ameliorate refractive errors developing in children. Recent findings Increasing evidence implicates diurnal and circadian rhythms in eye growth and refractive error development. In both humans and animals, ocular length and other anatomical and physiological features of the eye undergo diurnal oscillations. Systemically, such rhythms are primarily generated by the ‘master clock’ in the surpachiasmatic nucleus, which receives input from the intrinsically photosensitive retinal ganglion cells (ipRGCs) through the activation of the photopigment melanopsin. The retina also has an endogenous circadian clock. In laboratory animals developing experimental myopia, oscillations of ocular parameters are perturbed. Retinal signaling is now believed to influence refractive development; dopamine, an important neurotransmitter found in the retina, not only entrains intrinsic retinal rhythms to the light:dark cycle, but it also modulates refractive development. Circadian clocks comprise a transcription/translation feedback control mechanism utilizing so-called clock genes that have now been associated with experimental ametropias. Contemporary clinical research is also reviving ideas first proposed in the nineteenth century that light exposures might impact refraction in children. As a result, properties of ambient lighting are being investigated in refractive development. In other areas of medical science, circadian dysregulation is now thought to impact many non-ocular disorders, likely because the patterns of modern artificial lighting exert adverse physiological effects on circadian pacemakers. How, or if, such modern light exposures and circadian dysregulation contribute to refractive development is not known. Summary The premise of this review is that circadian biology could be a productive area worthy of increased investigation, which might lead to the improved understanding of refractive development and improved therapeutic interventions.

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Alterations of Glutamate and γ-Aminobutyric Acid Expressions in Normal and Myopic Eye Development in Guinea Pigs

Abstract: Taken together, our findings suggest that the RGG has a pivotal role in eye development and myopia. The abnormal retina signal induced by the unbalanced ratio between Glu and GABA is related closely to the occurrence of myopia.

Cited by 21 publications

References 62 publications

Analysis of Multifactor-Driven Myopia Disease Modules to Guide Personalized Treatment and Drug Development

Analysis of Multifactor-Driven Myopia Disease Modules to Guide Personalized Treatment and Drug Development

Short term optical defocus perturbs normal developmental shifts in retina/RPE protein abundance

Circadian rhythms, refractive development, and myopia

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