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Daily Patterns of Retinal and Choroidal Gene Expression and Circadian Biology in Myopia Pathogenesis

ABSTRACT: Daily Patterns of Retinal and Choroidal Gene Expression and Circadian Biology in Myopia Pathogenesis

PROVIDER: PRJNA946718 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23921200.fastq.gz	Fastqsanger.gz
	SRR23921300.fastq.gz	Fastqsanger.gz
	SRR23921400.fastq.gz	Fastqsanger.gz
	SRR23921500.fastq.gz	Fastqsanger.gz
	SRR23921600.fastq.gz	Fastqsanger.gz

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Daily Patterns of Retinal and Choroidal Gene Expression and Circadian Biology in Myopia Pathogenesis

Project description:We investigated diurnal changes in gene expression in the retina and choroid at the onset of experimental myopia. We induced visual form deprivation myopia in young chicks, and isolated retinal and choroidal tissues separately in form- deprived and contralateral control eyes every 4 hours over a single 24-hour period.

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Diurnal Retinal and Choroidal Gene Expression Patterns Distinguish Myopia Progression from Myopia Onset

Project description:Following laboratory and clinical findings implicating circadian biology in the pathogenesis of myopia (nearsightedness), we examined gene expression in two crucial tissues controlling post-natal refractive development, the retina and choroid. Inducing unilateral visual form deprivation myopia in young chicks, a widely studied and validated model, we isolated retinal and choroidal tissues every 4 hours over a single day from myopic and contralateral control eyes during a period time when myopia progresses rapidly.

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Diurnal Retinal and Choroidal Gene Expression Patterns Distinguish Myopia Progression from Myopia Onset

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Diurnal retinal and choroidal gene expression patterns support a role for circadian biology in myopia pathogenesis.

Project description:The prevalence of myopia (nearsightedness) is increasing to alarming levels, but its etiology remains poorly understood. Because both laboratory and clinical findings suggest an etiologic role for circadian rhythms in myopia development, we assayed gene expression by RNA-Seq in retina and choroid at the onset of unilateral experimental myopia in chick, isolating tissues every 4 h during a single 24-h period from myopic and contralateral control eyes. Occluded versus open eye gene expression differences varied considerably over the 24-h sampling period, with some occurring at multiple times of day but with others showing differences at only a single investigated timepoint. Some of the genes identified in retina or choroid of chick myopia were previously identified as candidate genes for common human myopia. Like differentially expressed genes, pathways identified by Gene Set Enrichment Analysis also varied dramatically by sampling time. Considered with other laboratory data, human genetic and epidemiology data, these findings further implicate circadian events in myopia pathogenesis. The present results emphasize a need to include time of day in mechanistic studies of myopia and to assess circadian biology directly in trying to understand better the origin of myopia and to develop more effective therapies.

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RNA analysis of the circadian rhythm of choroidal neovascularization

Project description:Many diseases that affect the heart, brain, and even the eyes originate from vascular pathology, emphasizing the role of vascular regulation. In age-related macular degeneration (AMD), excessive growth of abnormal blood vessels in the eye (choroidal neovascularization) ultimately leads to detachment of retinal pigment epithelium and decreased vision, indicating the importance of choroidal neovascularization in the treatment of age-related diseases. The circadian clock in the mammalian retina regulates various retinal functions, enabling the retina to adapt to the light dark cycle. Emerging evidence suggests a link between circadian clock and retinopathy, but the causal relationship has not yet been determined.

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Project description:Introduction: The mechanisms underlying myopia and myopia-related retinopathy remain not fully understood. We proposed to examine the function and underlying mechanisms of miR-204-5p in myopia development. Methods: The miR-204-5p expression level was assessed in the vitreous humor (VH) of a cohort consisting of 11 patients with high myopia (HM) and 16 control patients undergoing retinal surgery. The functional implications of miR-204-5p in ARPE-19 cells were assessed, encompassing cell aggressiveness. Thioredoxin-interacting protein (TXNIP) was found as a possible target of miR-204-5p through mRNA sequencing, and its interaction with miR-204-5p was confirmed employing luciferase assay and western blotting. Furthermore, the miR-204-5p function in regulating oxidative stress was examined by measuring reactive oxygen species (ROS) accumulation. Results: miR-204-5p was found to be significantly reduced in the VH of HM patients. Overexpression of miR-204-5p suppressed cell proliferation, migration, invasion, and apoptosis in ARPE-19 cells. The bioinformatics analysis demonstrated that miR-204-5p can modulate the genes associated with pathways relevant to myopia, including glycosaminoglycan (GAG) degradation, lysosome, and TGF−beta signaling pathway. The direct targeting of miR-204-5p on TXNIP has been confirmed through validation, and its downregulation mediated the miR-204-5p impacts on ARPE-19 cells. Moreover, miR-204-5p overexpression significantly reduced ROS accumulation by targeting TXNIP. Conclusion: Our findings revealed the possible contribution of the miR-204-5p/TXNIP axis in myopia development by regulating oxidative stress, which may provide new targets and novel therapeutic strategies to combat this prevalent and debilitating condition.

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Large-scale microRNA expression profiling identifies retinal miRNA-mRNA signaling pathways underlying form-deprivation myopia in mice

Project description:Development of myopia is associated with large-scale changes in ocular tissue gene expression. Although differential expression of coding genes underlying development of myopia has been a subject of intense investigation, the role of non-coding genes such as microRNAs in the development of myopia is largely unknown. In this study, we explored myopia-associated miRNA expression profiles in the retina and sclera of C57Bl/6J mice with experimentally induced myopia using microarray technology. We found a total of 53 differentially expressed miRNAs in the retina and no differences in miRNA expression in the sclera of C57BL/6J mice after 10 days of visual form deprivation, which induced -6.93 ± 2.44 D (p < 0.000001, n = 12) of myopia. We also identified their putative mRNA targets among mRNAs found to be differentially expressed in myopic retina and potential signaling pathways involved in the development of form-deprivation myopia using miRNA-mRNA interaction network analysis. Analysis of myopia-associated signaling pathways revealed that myopic response to visual form deprivation in the retina is regulated by a small number of highly integrated signaling pathways. Our findings highlight substantial involvement of miRNAs in the regulation of refractive eye development, and in the development of myopia through the retinal gene regulation.

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MiR-204-5p may Regulate Oxidative Stress in Myopia and Myopia-Related Retinopathy

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