Cyclic Adenosine Monophosphate Activates Retinal Apolipoprotein A1 Expression and Inhibits Myopic Eye Growth

Chun, Rachel Ka Man; Shan, Sze Wan; Lam, Thomas Chuen; Wong, Cho Lee; Li, King Kit; Wai, Chi; To, Chi‐Ho

doi:10.1167/iovs.14-14233

Cited by 13 publications

(8 citation statements)

References 36 publications

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“…MiR-15b and miR-16 have been shown to play a role in suppressing insulin resistance by reducing TNF α and SOCS3 signaling and increasing IGFBP-3 expression. This protects the retinal endothelial cells (REC) against hyperglycemia-induced apoptosis and has been identified as a potential therapeutic target for the treatment of diabetic retinopathy [ 48 ].…”

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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“…14,17 A recent study demonstrated that stimulation of cAMPdependent protein kinase induced by 8-Br-cAMP intravitreal injections reduced myopia progression in a negative lensinduced model to such an extent that it resulted in a hyperopic refraction in chicks. 34 This study also showed that positive lens defocus inhibited ocular growth and increased both retinal cAMP and ApoA1 levels. These results differ from those previously reported by our group, in which the putative rise in scleral cAMP levels induced by FSK had no additional effect on the refraction induced by FD, and the retinal cAMP levels were unaltered in these guinea pigs.…”

Section: Discussionmentioning

confidence: 60%

Role of Cyclic Adenosine Monophosphate in Myopic Scleral Remodeling in Guinea Pigs: A Microarray Analysis

Srinivasalu

Pan

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…Aspartate receptors were implicated in myopia development by at least two studies [ 60 , 61 ]. Nitric oxide and cAMP signaling were also suggested to play a role in the development of myopia by several studies in chickens [ 37 – 39 ]. Dopamine signaling has long been associated with experimental myopia and refractive eye development [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth

et al. 2018

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Myopia (nearsightedness) is the most common eye disorder, which is rapidly becoming one of the leading causes of vision loss in several parts of the world because of a recent sharp increase in prevalence. Nearwork, which produces hyperopic optical defocus on the retina, has been implicated as one of the environmental risk factors causing myopia in humans. Experimental studies have shown that hyperopic defocus imposed by negative power lenses placed in front of the eye accelerates eye growth and causes myopia, whereas myopic defocus imposed by positive lenses slows eye growth and produces a compensatory hyperopic shift in refractive state. The balance between these two optical signals is thought to regulate refractive eye development; however, the ability of the retina to recognize the sign of optical defocus and the composition of molecular signaling pathways guiding emmetropization are the subjects of intense investigation and debate. We found that the retina can readily distinguish between imposed myopic and hyperopic defocus, and identified key signaling pathways underlying retinal response to the defocus of different signs. Comparison of retinal transcriptomes in common marmosets exposed to either myopic or hyperopic defocus for 10 days or 5 weeks revealed that the primate retina responds to defocus of different signs by activation or suppression of largely distinct pathways. We also found that 29 genes differentially expressed in the marmoset retina in response to imposed defocus are localized within human myopia quantitative trait loci (QTLs), suggesting functional overlap between genes differentially expressed in the marmoset retina upon exposure to optical defocus and genes causing myopia in humans. These findings identify retinal pathways involved in the development of myopia, as well as potential new strategies for its treatment.

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Cyclic Adenosine Monophosphate Activates Retinal Apolipoprotein A1 Expression and Inhibits Myopic Eye Growth

Abstract: The 8-Br-cAMP robustly inhibited development of lens-induced myopia. The increase in retinal ApoA1 observed in cAMP-treated and hyperopic eyes suggested a possible interplay between ApoA1 and cAMP in regulating eye growth.

Cited by 13 publications

References 36 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

Role of Cyclic Adenosine Monophosphate in Myopic Scleral Remodeling in Guinea Pigs: A Microarray Analysis

Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth

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