Small RNA Sequencing of Aqueous Humor and Plasma in Patients With Primary Open-Angle Glaucoma

Hubens, Wouter; Krauskopf, Julian; Beckers, Henny J. M.; Kleinjans, Jos; Webers, Carroll A.B.; Gorgels, Theo G. M. F.

doi:10.1167/iovs.62.7.24

Cited by 23 publications

(18 citation statements)

References 71 publications

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“…Recent studies that have focused on the roles of miRNAs in modulating the biological functions of the TM contribute to identifying more biomarkers for the treatment of glaucoma [ 27 , 41 ]. It was demonstrated by Hubens et al that hsa-miR-486-5p has a downregulated level in glaucoma patients [ 29 ]. In the lens, miR-486-5p targets SMAD2 to repress TGF- β 2-induced ECM remodeling [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

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miR-486-5p Restrains Extracellular Matrix Production and Oxidative Damage in Human Trabecular Meshwork Cells by Targeting TGF-β/SMAD2 Pathway

Zhang

Long

et al. 2022

Journal of Ophthalmology

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Background. Glaucoma is characterized by elevated intraocular pressure caused by aqueous outflow dysfunction. Trabecular meshwork plays a key role in controlling intraocular pressure by modulating aqueous outflow. This study investigated the protective effects of miR-486-5p in H2O2-stimulated human trabecular meshwork cells (TMCs). Methods. TMCs were disposed with 300 μM H2O2 to establish oxidative damage models in vitro. miR-486-5p mimics and its controls were transfected into TMCs, and cell apoptosis and extracellular matrix production (ECM) genes were measured by flow cytometry, western blotting, and immunofluorescence staining. Activities of superoxide dismutase (SOD) and malondialdehyde (MDA) were also assayed. Online tools and luciferase reporter assays were used to uncover the relationship between miR-486-5p and the TGF-β/SMAD2 pathway. Results. We found that H2O2-induced oxidative damage in TMCs and miR-486-5p was downregulated in H2O2-stimulated TMCs. Overexpression of miR-486-5p mitigated H2O2-induced oxidative damage by inhibiting apoptosis, reducing cleaved caspase-3/9 expression, reducing MDA levels, and increasing SOD levels as well as downregulating ECM genes. SMAD2 was demonstrated to be targeted by miR-486-5p, and miR-486-5p inhibited TGF-β/SMAD2 signaling in H2O2-stimulated TMCs. Additionally, SMAD2 was upregulated by H2O2, and SMAD2 upregulation abrogated the protective effects of miR-486-5p against H2O2-induced injury. Conclusion. miR-486-5p restrains H2O2-induced oxidative damage in TMCs by targeting the TGF-β/SMAD2 pathway.

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Section: Discussionmentioning

confidence: 99%

“…Small RNA sequencing results showed that miR-486-5p was downregulated in the aqueous humor of glaucoma patients [ 29 ]. Moreover, miR-486-5p was shown to inhibit TGF- β 2-mediated ECM remodeling via inhibition of SMAD2 [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

miR-486-5p Restrains Extracellular Matrix Production and Oxidative Damage in Human Trabecular Meshwork Cells by Targeting TGF-β/SMAD2 Pathway

Zhang

Long

et al. 2022

Journal of Ophthalmology

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“…As MR analysis can imply causality between an exposure and an outcome, next we explored the possibility of using these two high-confidence miRNAs as biomarkers for COVID-19 severity. For whole blood/serum samples, both high-confidence miRNAs have been explored as potential biomarkers for different health conditions [ 38 , 39 ]. For RNA-sequencing profiling in peripheral blood mononuclear cells (PBMCs), the potential of these two miRNAs as biomarkers has not been investigated.…”

Section: Discussionmentioning

confidence: 99%

Identifying Putative Causal Links between MicroRNAs and Severe COVID-19 Using Mendelian Randomization

Song³

et al. 2021

Cells

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The SARS-CoV-2 (COVID-19) pandemic has caused millions of deaths worldwide. Early risk assessment of COVID-19 cases can help direct early treatment measures that have been shown to improve the prognosis of severe cases. Currently, circulating miRNAs have not been evaluated as canonical COVID-19 biomarkers, and identifying biomarkers that have a causal relationship with COVID-19 is imperative. To bridge these gaps, we aim to examine the causal effects of miRNAs on COVID-19 severity in this study using two-sample Mendelian randomization approaches. Multiple studies with available GWAS summary statistics data were retrieved. Using circulating miRNA expression data as exposure, and severe COVID-19 cases as outcomes, we identified ten unique miRNAs that showed causality across three phenotype groups of COVID-19. Using expression data from an independent study, we validated and identified two high-confidence miRNAs, namely, hsa-miR-30a-3p and hsa-miR-139-5p, which have putative causal effects on developing cases of severe COVID-19. Using existing literature and publicly available databases, the potential causative roles of these miRNAs were investigated. This study provides a novel way of utilizing miRNA eQTL data to help us identify potential miRNA biomarkers to make better and early diagnoses and risk assessments of severe COVID-19 cases.

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“…The exact pathological mechanisms underlying glaucoma remain unclear. It is believed that the pathological process of glaucoma is related to intraocular pressure, age, and genetic factors [ 60 ]. Thus, exploring the factors influencing glaucoma, including miRNAs, is critical.…”

Section: Applications Of Hts Technology In Ocular Diseasesmentioning

confidence: 99%

“…In addition, thiamine and purine metabolism pathways related to the differential expression of miRNAs may play a role in the occurrence and development of optic neuropathy in glaucoma [ 58 ]. After conducting small-molecule RNA sequencing of aqueous humor and plasma of patients with POAG, Hubens et al found that there was no differential miRNA expression in plasma, but there were four upregulated miRNAs (hsa-miR-30a-3p, hsa-miR-143-3p, hsa-miR-211-5p, and hsa-miR221-3p) and three downregulated miRNAs (hsa-miR-92a-3p, hsa-miR-451a, and hsa-miR-486-5p) in the aqueous humor [ 60 ]. The study suggested that hsa-miR-221-3p and hsa-miR-143-3p, the miRNAs upregulated in the aqueous humor, are potential biomarkers for diagnosing glaucoma [ 60 ].…”

Section: Applications Of Hts Technology In Ocular Diseasesmentioning

confidence: 99%

Application Progress of High-Throughput Sequencing in Ocular Diseases

Zhang²,

Cao³

et al. 2022

JCM

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Ocular diseases affect multiple eye parts and can be caused by pathogenic infections, complications of systemic diseases, genetics, environment, and old age. Understanding the etiology and pathogenesis of eye diseases and improving their diagnosis and treatment are critical for preventing any adverse consequences of these diseases. Recently, the advancement of high-throughput sequencing (HTS) technology has paved wide prospects for identifying the pathogenesis, signaling pathways, and biomarkers involved in eye diseases. Due to the advantages of HTS in nucleic acid sequence recognition, HTS has not only identified several normal ocular surface microorganisms but has also discovered many pathogenic bacteria, fungi, parasites, and viruses associated with eye diseases, including rare pathogens that were previously difficult to identify. At present, HTS can directly sequence RNA, which will promote research on the occurrence, development, and underlying mechanism of eye diseases. Although HTS has certain limitations, including low effectiveness, contamination, and high cost, it is still superior to traditional diagnostic methods for its efficient and comprehensive diagnosis of ocular diseases. This review summarizes the progress of the application of HTS in ocular diseases, intending to explore the pathogenesis of eye diseases and improve their diagnosis.

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Small RNA Sequencing of Aqueous Humor and Plasma in Patients With Primary Open-Angle Glaucoma

Cited by 23 publications

References 71 publications

miR-486-5p Restrains Extracellular Matrix Production and Oxidative Damage in Human Trabecular Meshwork Cells by Targeting TGF-β/SMAD2 Pathway

miR-486-5p Restrains Extracellular Matrix Production and Oxidative Damage in Human Trabecular Meshwork Cells by Targeting TGF-β/SMAD2 Pathway

Identifying Putative Causal Links between MicroRNAs and Severe COVID-19 Using Mendelian Randomization

Application Progress of High-Throughput Sequencing in Ocular Diseases

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