Evaluation of silent information regulator T (SIRT) 1 and Forkhead Box O (FOXO) transcription factor 1 and 3a genes in glaucoma

Yaman, Derya; Takmaz, Tamer; Yüksel, Nilay; Dincer, Selin Akad; Şahin, Feride İffet

doi:10.1007/s11033-020-05994-3

Cited by 18 publications

(12 citation statements)

References 84 publications

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“… 50 We found that the number of SIRT1-postive cells was decreased in the iris of APAC eyes, similar to the results in a previous study where the expression of SIRT1 decreased significantly in the trabecular mesh of patients with high IOP glaucoma. 51 IL-6 and IL-8 levels were also elevated in the AqH of APAC eyes. Therefore oxidative stress-induced premature senescence may be involved in the damage and repair of iris atrophy ( Fig.…”

Section: Discussionmentioning

confidence: 87%

Occurrence of Oxidative Stress and Premature Senescence in the Anterior Segment of Acute Primary Angle-Closure Eyes

Shi

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose To explore whether oxidative stress and premature senescence occur in the anterior segment of acute primary angle-closure (APAC) eyes after increased intraocular pressure. Methods The eye samples of 21 APAC patients, 22 age-related cataract patients, and 10 healthy donors were included. Aqueous humor (AqH), iris, and anterior lens capsule samples were collected. The levels of oxidative stress markers and senescence-associated secretory phenotype (SASP)–related cytokines in AqH were estimated using relevant reagent kits and multiplex bead immunoassay technique. The intensity of relevant markers in anterior segment tissues was examined by immunofluorescence- and senescence-associated β-galactosidase (SA-β-gal) staining. Results Oxidative stress marker levels elevated significantly in the AqH of APAC eyes. Reactive oxygen species (ROS) and 8-hydroxydeoxyguanosine levels were positively correlated with preoperative peak intraocular pressure and age, whereas reduced glutathione/oxidized glutathione (GSH/GSSH) ratio was negatively correlated with both parameters. The levels of several SASP-related cytokines were markedly increased. ROS and malondialdehyde levels were positively correlated with the levels of some SASP-related cytokines, whereas superoxide dismutase level and GSH/GSSH ratio showed an opposite trend. The number of cells positive for oxidative mitochondrial DNA damage and apoptosis-related markers increased in the iris and anterior lens capsule of the APAC group. Senescence-associated markers (p16, p21, and p53) and SA-β-gal activity were increased in the iris of the APAC group. Conclusions Oxidative stress and premature senescence occurred in the anterior segment of APAC patients, suggesting that they may be involved in the development of pathological changes in the anterior segment of APAC eyes.

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Section: Discussionmentioning

confidence: 87%

Occurrence of Oxidative Stress and Premature Senescence in the Anterior Segment of Acute Primary Angle-Closure Eyes

Shi

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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“…For example, SIX6 risk variation, silent information regulator T (SIRT) 1, and Forkhead Box O (FOXO) transcription factor 1 and 3a ( FOXOs 1 –3a), which is the key to the pathogenesis of glaucoma or optic nerve degeneration [ 29 , 30 ]. Furthermore, the target gene and its relationship with miRNA and signal pathway can realize the diagnosis of glaucoma [ 31 ], lncRNA and miRNA have also been proved to be key to glaucoma diagnosis and retinal nerve regulation. For example, lncRNAs (DNAJC27-AS1, AF121898, OIP5-AS1, and SNX29P2) were established as hub RNAs in the ceRNA network of POAG [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Based on multiple machine learning to identify the ENO2 as diagnosis biomarkers of glaucoma

Dai

Kang

et al. 2022

BMC Ophthalmol

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Purpose Glaucoma is a generic term of a highly different disease group of optic neuropathies, which the leading cause of irreversible vision in the world. There are few biomarkers available for clinical prediction and diagnosis, and the diagnosis of patients is mostly delayed. Methods Differential gene expression of transcriptome sequencing data (GSE9944 and GSE2378) for normal samples and glaucoma samples from the GEO database were analyzed. Furthermore, based on different algorithms (Logistic Regression (LR), Random Forest (RF), lasso regression (LASSO)) two diagnostic models are constructed and diagnostic markers are screened. GO and KEGG analyses revealed the possible mechanism of differential genes in the pathogenesis of glaucoma. ROC curve confirmed the effectiveness. Results LR-RF model included 3 key genes (NAMPT, ADH1C, ENO2), and the LASSO model outputted 5 genes (IFI16, RFTN1, NAMPT, ADH1C, and ENO2), both algorithms have excellent diagnostic efficiency. ROC curve confirmed that the three biomarkers ADH1C, ENO2, and NAMPT were effective in the diagnosis of glaucoma. Next, the expression analysis of the three diagnostic biomarkers in glaucoma and control samples confirmed that NAMPT and ADH1C were up-regulated in glaucoma samples, and ENO2 was down-regulated. Correlation analysis showed that ENO2 was significantly negatively correlated with ADH1C (cor = -0.865714202) and NAMPT (cor = -0.730541227). Finally, three compounds for the treatment of glaucoma were obtained in the TCMs database: acetylsalicylic acid, 7-o-methylisomucitol and scutellarin which were applied to molecular docking with the diagnostic biomarker ENO2. Conclusions In conclusion, our research shows that ENO2, NAMPT, and ADH1C can be used as diagnostic markers for glaucoma, and ENO2 can be used as a therapeutic target.

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“…47 Interestingly, a decreased expression of SIRT1 has been observed in the TM of glaucoma patients. 48 Upregulation of hsa-miR-221-3p is also pro-apoptotic in ocular tissue, as shown by two studies with lens epithelial cells of cataract patients. 49,50 Further studies are required to assess whether hsa-miR-211-5p and hsa-miR-221-3p circulating in AH can indeed exert a proapoptotic effect on TM cells or if they reflect the increased apoptosis of RGCs.…”

Section: Biological Function Of the Differentially Expressed Mirnasmentioning

confidence: 95%

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

Hubens

Krauskopf

Beckers

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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Identify differentially expressed microRNAs (miRNAs) in aqueous humor (AH) and blood of primary open-angle glaucoma (POAG) patients by using small RNA sequencing. These may provide insight into POAG pathophysiology or serve as diagnostic biomarker.METHODS. AH and plasma of nine POAG patients and 10 cataract control patients were small RNA sequenced on Illumina NovaSeq 6000. Identification of gene transcripts targeted by differentially expressed miRNAs was done with miRWalk and MirPath. These targets were used for pathway analysis and Gene Ontology enrichment. Diagnostic potential was evaluated by receiver operating characteristics analysis. RESULTS.We identified 715 miRNAs in plasma and 62 miRNAs in AH. Plasma miRNA profile did not differ between POAG and control. In contrast, in AH, seven miRNAs were differentially expressed. Hsa-miR-30a-3p, hsa-miR-143-3p, hsa-miR-211-5p, and hsa-miR-221-3p were upregulated, whereas hsa-miR-92a-3p, hsa-miR-451a, and hsa-miR-486-5p were downregulated in POAG. Compared to previous studies, hsa-mir-143-3p, hsa-miR-211-5p, and hsa-miR-221-3p were reported previously, strengthening their involvement in POAG whereas hsa-miR-30a-3p, hsa-miR-92a-3p, and hsa-miR-486-5p are implicated in POAG for the first time. Identified gene transcripts were involved in several pathways, some implicated in glaucoma before (e.g., TGF-β and neurotrophin signaling), whereas others are new (e.g., prolactin and apelin signaling). In respect to diagnostics, AH concentration of hsa-mir-143-3p had an area under the curve (AUC) of 0.889. Combined with hsa-miR-221-3p, AUC improved to 0.96. CONCLUSIONS.Small RNA sequencing identified seven differentially expressed miRNAs in AH of POAG patients. The differentially expressed miRNAs may be useful as POAG biomarkers or could become targets for new therapeutic strategies.

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Evaluation of silent information regulator T (SIRT) 1 and Forkhead Box O (FOXO) transcription factor 1 and 3a genes in glaucoma

Cited by 18 publications

References 84 publications

Occurrence of Oxidative Stress and Premature Senescence in the Anterior Segment of Acute Primary Angle-Closure Eyes

Occurrence of Oxidative Stress and Premature Senescence in the Anterior Segment of Acute Primary Angle-Closure Eyes

Based on multiple machine learning to identify the ENO2 as diagnosis biomarkers of glaucoma

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

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