Pathogenesis and prospects for therapeutic clinical application of noncoding RNAs in glaucoma: Systematic perspectives

Rong, Rong; Wang, Mengxiao; You, Mengling; Li, Haibo; Xia, Xiaobo; Ji, Dan

doi:10.1002/jcp.30347

Cited by 13 publications

(10 citation statements)

References 159 publications

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“…In this study, we initially identified a few lncRNAs that may play a role in the pathogenesis of glaucoma, but did not delve into the mechanisms by which these lncRNAs are involved in the pathogenesis of glaucoma, which is an area that needs to be further explored in the future. lncRNAs are involved in the pathogenesis of glaucoma in three main ways, in addition to regulating the function of trabecular meshwork cells, participating in ECM and scar formation after glaucoma filtration surgery, and directly regulating RGC damage (37).It has been demonstrated that lncRNA may serve as a potential biomarker for primary open-angle glaucoma (38)(39)(40), and studies on the mechanism of lncRNA have mainly focused on the ceRNA mechanism. Several studies have demonstrated that lncRNA can regulate the loss of retinal ganglion cells (41-44), apoptosis of human trabecular meshwork cells and extracellular matrix deposition through the ceRNA mechanism (45-48).…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of long non-coding RNAs and mRNAs associated with glaucoma in vitro

You

Rong²,

Zeng³

et al. 2023

Front. Endocrinol.

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IntroductionIn recent years, the biological functions and important roles of long non-coding RNAs (lncRNAs) have been widely reported in many diseases. Although glaucoma is the leading cause of blindness worldwide, the specific mechanisms of lncRNAs in the pathogenesis and progression of glaucoma remain unclear. Our research aims to elucidate the differentially expressed lncRNAs and mRNAs in glaucoma and to provide a basis for further exploration of the specific mechanism of action of lncRNAs in the progression of glaucoma.MethodsWe performed RNA sequencing on samples from a pressurized model of R28 cells and performed bioinformatics analyses on the sequencing results. The expression consistency of lncRNAs in clinical samples from patients with glaucoma or cataracts was detected using real-time quantitative polymerase chain reaction (RT-qPCR).ResultsRNA sequencing results showed that lncRNAs in cluster 5 were upregulated with increasing stress after typing all significantly altered lncRNAs using k-means in a cellular stress model. KEGG analysis indicated that they were associated with neurodegenerative diseases. Differentially expressed lncRNAs were verified by RT-qPCR, and the lncRNA expression levels of AC120246.2 and XLOC_006247 were significantly higher in the aqueous humor (AH) of patients with glaucoma than in those with cataracts. For LOC102551819, there was almost no expression in the AH and trabecular meshwork in patients with glaucoma but high expression was observed in the iris. ConclusionOur research proposes potential diagnostic or intervention targets for clinical applications as well as a theoretical basis for more in-depth research on the function of lncRNAs in glaucoma.

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Section: Discussionmentioning

confidence: 99%

Integrated analysis of long non-coding RNAs and mRNAs associated with glaucoma in vitro

You

Rong²,

Zeng³

et al. 2023

Front. Endocrinol.

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“…miRNAs are tissue-specific and expressed in ocular tissues related to glaucoma [ 35 ]. Several studies have highlighted the significant role of miRNAs and their plausible underlying mechanisms in different types of glaucoma, including PXG [ 8 , 36 , 37 , 38 , 39 , 40 ]. Rao et al reported the overexpression of 12 miRNAs in PXG, of which miR-122-5p, miR-124-3p, and miR-424-5p targeted TGFβ1, fibrosis/ECM, and proteoglycan metabolism pathways [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Increasing evidence suggests the critical roles of microRNA (miRNA) in glaucoma [ 7 , 8 ]. miRNAs are small (~22 bp), conserved, noncoding RNAs that act by binding to complementary sequences in the 3′ untranslated region (3′ UTR) of messenger RNAs (mRNAs) to regulate posttranscriptional gene expression or translational repression [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Polymorphism rs3742330 in microRNA Biogenesis Gene DICER1 Is Associated with Pseudoexfoliation Glaucoma in Saudi Cohort

Kondkar

Azad

Sultan

et al. 2022

Genes

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We investigated the association between DICER1 (rs3742330) and DROSHA (rs10719) polymorphisms and pseudoexfoliation glaucoma (PXG) and related clinical phenotypes in a Saudi cohort. In a retrospective case-control study, TaqMan real-time, PCR-based genotyping was performed in 340 participants with 246 controls and 94 PXG cases. The minor (G) allele frequency of rs3742330 in PXG (0.03) was significantly different from that in the controls (0.08) and protective against PXG (odds ratio (OR) = 0.38, 95% confidence interval (CI) = 0.16–0.92), p = 0.017). Similarly, the rs3742330 genotypes showed a significant protective association with PXG in dominant (p = 0.019, OR = 0.38, 95% CI = 0.15–0.92), over-dominant (p = 0.024, OR = 0.39, 95% CI = 0.16–0.95), and log-additive models (p = 0.017, OR = 0.38, 95% CI = 0.16–0.92). However, none remained significant after an adjustment for age, sex, and multiple testing. Rs10719 in DROSHA did not show any significant allelic or genotype association with PXG. However, a protective effect of the GA haplotype in DICER1 and DROSHA and PXG (p = 0.034) was observed. Both polymorphisms showed no significant effect on intraocular pressure and the cup–disk ratio. In conclusion, we report a significant genetic association between variant rs3742330 in DICER1, a gene involved in miRNA biogenesis, and PXG. Further investigation in a larger group of patients of different ethnicities and functional studies are warranted to replicate and validate its potential role in PXG.

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“…Similar findings have been reported in another study using a model of H 2 O 2 -induced oxidative stress in HTM cells. Oxidative stress conditions in HTM cells significantly upregulated SNORD3A [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Small Nucleolar RNAs in Pseudoexfoliation Glaucoma

Gasińska

Czop

Kosior‐Jarecka

et al. 2022

Cells

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Small nucleolar RNAs (snoRNAs) are small non-coding regulatory RNAs that have been investigated extensively in recent years. However, the relationship between snoRNA and glaucoma is still unknown. This study aims to analyze the levels of snoRNA expression in the aqueous humor (AH) of patients with pseudoexfoliation glaucoma (PEXG) compared to a control group and identify hypothetical snoRNA-dependent mechanisms contributing to PEXG. The AH was obtained from eighteen Caucasian patients, comprising nine PEXG and nine age-matched control patients. RNA was isolated, and a microarray system was used to determine the snoRNA expression profiles. Functional and enrichment analyses were performed. We identified seven snoRNAs, SNORD73B, SNORD58A, SNORD56, SNORA77, SNORA72, SNORA64, and SNORA32, in the AH of the PEXG and control group patients. Five snoRNAs showed statistically significantly lower expression in the PEXG group, and two snoRNAs had statistically significantly higher expression in the PEXG group compared to the control group. In addition, we identified two factors—CACNB3 for SNORA64 and TMEM63C for SNORA32, similar to PEX-related genes (CACNA1A and TMEM136). The enrichment analysis for four genes targeted by snoRNAs revealed possible mechanisms associated with glaucoma and/or PEX, but the direct role of snoRNAs in these biological processes was not proven.

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Pathogenesis and prospects for therapeutic clinical application of noncoding RNAs in glaucoma: Systematic perspectives

Cited by 13 publications

References 159 publications

Integrated analysis of long non-coding RNAs and mRNAs associated with glaucoma in vitro

Integrated analysis of long non-coding RNAs and mRNAs associated with glaucoma in vitro

Polymorphism rs3742330 in microRNA Biogenesis Gene DICER1 Is Associated with Pseudoexfoliation Glaucoma in Saudi Cohort

Small Nucleolar RNAs in Pseudoexfoliation Glaucoma

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