Molecular Vision最新文献

{"title":"Basement membrane regeneration and TGF-β1 expression in rabbits with corneal perforating injury.","authors":"Na Meng,&nbsp;Jinling Wu,&nbsp;Jingjing Chen,&nbsp;Yuqing Luo,&nbsp;Luxing Xu,&nbsp;Xia Li","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the relationship between basement membrane (BM) regeneration and the spatiotemporal expression of TGF-β1 during wound healing in rabbits with corneal perforating injury.</p><p><strong>Methods: </strong>Forty-two rabbits were randomly allocated into 7 experimental groups, with 6 rabbits per group at each time point. The central cornea of the left eye was injured with 2.0 mm trephine to establish the perforating injury model. Six rabbits that received no treatment were used as controls. The cornea was evaluated at 3 days, 1-3 weeks, and 1-3 months after injury with a slit lamp for haze levels. Real-time quantitative polymerase chain reaction (qRT-PCR) was performed to quantify the relative expression of TGF-β1 and α-SMA mRNA. Immunofluorescence (IF) was used to assess TGF-β1 and alpha-smooth actin (α-SMA) expression and localization. BM regeneration was assessed using transmission electron microscopy (TEM).</p><p><strong>Results: </strong>After injury, dense haze appeared at 1 month and then gradually faded. The relative expression of TGF-β1 mRNA peaked at 1 week and then decreased until 2 months. The relative α-SMA mRNA expression reached its peak at 1 week, then reached a small peak again at 1 month. IF results showed that TGF-β1 was initially detected in the fibrin clot at 3 days and then in the entire repairing stroma at 1 week. TGF-β1 localization gradually diminished from the anterior region to the posterior region at 2 weeks to 1 month, and it was nearly absent at 2 months. The myofibroblast marker α-SMA was observed in the entire healing stroma at 2 weeks. Localization of α-SMA gradually disappeared from the anterior region at 3 weeks to 1 month, remaining only in the posterior region at 2 months and disappearing at 3 months. Defective epithelial basement membrane (EBM) was first detected at 3 weeks after injury, then gradually repaired, and was nearly regenerated at 3 months. A thin and uneven Descemet's membrane (DM) was initially detected at 2 months after injury, then gradually regenerated to some extent, but remained abnormal at 3 months.</p><p><strong>Conclusions: </strong>In the rabbit corneal perforating injury model, EBM regeneration was observed earlier than DM. At 3 months, complete EBM regeneration was observed, while the regenerated DM was still defective. TGF-β1 was distributed throughout the entire wound area in the early stages and then decreased from the anterior to the posterior region. α-SMA exhibited a similar temporospatial expression to TGF-β1. EBM regeneration may play a key role in low expression of TGF-β1 and α-SMA in the anterior stroma. Meanwhile, incomplete DM regeneration may contribute to the sustained expression of TGF-β1 and α-SMA in the posterior stroma.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"29 ","pages":"58-67"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3e/87/mv-v29-58.PMC10243679.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9600055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphological, biochemical, and transcriptomic characterization of iPSC-derived human RPE cells from normal and Smith-Lemli-Opitz syndrome patients.","authors":"Michael H Farkas, Lara A Skelton, Sriganesh Ramachandra-Rao, Elizabeth Au, Steven J Fliesler","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"28 ","pages":"394-411"},"PeriodicalIF":1.8,"publicationDate":"2022-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/b8/mv-v28-394.PMC9744241.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10447356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sulforaphane recovers cone function in an Nrf2-dependent manner in middle-aged mice undergoing RPE oxidative stress.","authors":"Xiaoping Qi,&nbsp;Dorothy A Walton,&nbsp;Kendra S Plafker,&nbsp;Michael E Boulton,&nbsp;Scott M Plafker","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables that has therapeutic efficacy in numerous animal models of human disease, including mouse models of retinal degeneration. However, despite dozens of clinical trials, the compound remains to be tested as a clinical treatment for ocular disease. Numerous cellular activities of SFN have been identified, including the activation of Nrf2, a transcription factor that induces a battery of target gene products to neutralize oxidative and xenobiotic stresses. As Nrf2 expression and function reportedly decrease with aging, we tested whether the loss of the transcription factor limits the therapeutic efficacy of SFN against retinal degeneration.</p><p><strong>Methods: </strong>Six- to 8-month-old wild-type and Nrf2 knockout mice were treated with SFN beginning 1 month after ribozyme-mediated knockdown of superoxide dismutase 2 (SOD2) mRNA in the RPE. The impacts of MnSOD (the protein product of SOD2) knockdown and the efficacy of SFN were evaluated using a combination of electroretinography (ERG), spectral domain optical coherence tomography (SD-OCT), and postmortem histology.</p><p><strong>Results: </strong>SFN restored the ERG photopic b-wave suppressed by MnSOD loss in wild-type mice, but not in the Nrf2 knockout mice. In contrast, ERG scotopic a- and b-wave loss was not restored for either genotype. SFN significantly improved retinal thickness in the Nrf2 knockout mice with MnSOD knockdown, but this was not observed in the wild-type mice. In both genotypes, SFN treatment reduced morphological markers of RPE atrophy and degeneration, although these improvements did not correlate proportionally with functional recovery.</p><p><strong>Conclusions: </strong>These findings highlight the capacity of SFN to preserve cone function, as well as the potential challenges of using the compound as a standalone treatment for age-related retinal degeneration under conditions associated with reduced Nrf2 function.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":" ","pages":"378-393"},"PeriodicalIF":2.2,"publicationDate":"2022-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bd/4e/mv-v28-378.PMC9603948.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40447723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation efficiency of collagenase and EDTA for the culture of corneal endothelial cells.","authors":"Kim Santerre,&nbsp;Stéphanie Proulx","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Tissue engineering of the corneal endothelium, as well as cell therapy, has been proposed as an alternative approach for the treatment of corneal endotheliopathies. These approaches require in vitro amplification of functional corneal endothelial cells (CECs). The goal of this study was to compare two common isolation methods, collagenase A and EDTA (EDTA), and determine whether they influence cell viability, morphology, and barrier function.</p><p><strong>Methods: </strong>Human eye bank research-grade corneas were used to isolate and cultivate CECs. All donors were more than 40 years old. Two Descemet membranes from the same donor were used separately to compare the collagenase A and EDTA cell isolation methods. The number of isolated cells, cell viability, morphology, and barrier functionality were compared.</p><p><strong>Results: </strong>A higher isolation efficiency of viable CECs and a higher circularity index (endothelial morphology) were obtained using collagenase A. Passage 3 cells presented similar barrier functionalities regardless of the isolation method.</p><p><strong>Conclusions: </strong>This study showed that isolation of CECs using collagenase A yields higher isolation efficiency than EDTA, delaying the loss of endothelial morphology for early passage cells.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":" ","pages":"331-339"},"PeriodicalIF":2.2,"publicationDate":"2022-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c6/8c/mv-v28-331.PMC9603909.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40457318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral administration of a dual ET_A/ET_B receptor antagonist promotes neuroprotection in a rodent model of glaucoma.","authors":"Bindu Kodati,&nbsp;Nolan R McGrady,&nbsp;Hayden B Jefferies,&nbsp;Dorota L Stankowska,&nbsp;Raghu R Krishnamoorthy","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Glaucoma is a neurodegenerative disease associated with elevated intraocular pressure and characterized by optic nerve axonal degeneration, cupping of the optic disc, and loss of retinal ganglion cells (RGCs). The endothelin (ET) system of vasoactive peptides (ET-1, ET-2, ET-3) and their G-protein coupled receptors (ET_A and ET_B receptors) have been shown to contribute to the pathophysiology of glaucoma. The purpose of this study was to determine whether administration of the endothelin receptor antagonist macitentan was neuroprotective to RGCs and optic nerve axons when administered after the onset of intraocular pressure (IOP) elevation in ocular hypertensive rats.</p><p><strong>Methods: </strong>Male and female Brown Norway rats were subjected to the Morrison model of ocular hypertension by injection of hypertonic saline through the episcleral veins. Following IOP elevation, macitentan (5 mg/kg body wt) was administered orally 3 days per week, and rats with IOP elevation were maintained for 4 weeks. RGC function was determined by pattern electroretinography (PERG) at 2 and 4 weeks post-IOP elevation. Rats were euthanized by approved humane methods, and retinal flat mounts were generated and immunostained for the RGC-selective marker Brn3a. PPD-stained optic nerve sections were imaged by confocal microscopy. RGC and axon counts were conducted in a masked manner and compared between the treatment groups.</p><p><strong>Results: </strong>Significant protection against loss of RGCs and optic nerve axons was found following oral administration of macitentan in rats with elevated IOP. In addition, a protective trend for RGC function, as measured by pattern ERG analysis, was evident following macitentan treatment.</p><p><strong>Conclusions: </strong>Macitentan treatment had a neuroprotective effect on RGCs and their axons, independent of its IOP-lowering effect, suggesting that macitentan may complement existing treatments to prevent neurodegeneration during ocular hypertension. The findings presented have implications for the use of macitentan as an oral formulation to promote neuroprotection in glaucoma patients.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":" ","pages":"165-177"},"PeriodicalIF":2.2,"publicationDate":"2022-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ee/13/mv-v28-165.PMC9491150.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40663804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa-miR-150-5p inhibits Wnt-β-catenin signaling in human corneal epithelial stem cells.","authors":"Lavanya Kalaimani,&nbsp;Bharanidharan Devarajan,&nbsp;Venkatesh Prajna Namperumalsamy,&nbsp;Muthukkaruppan Veerappan,&nbsp;Julie T Daniels,&nbsp;Gowri Priya Chidambaranathan","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>In our earlier study, we identified hsa-miR-150-5p as a highly expressed miRNA in enriched corneal epithelial stem cells (CESCs). In this study, we aimed to understand the molecular regulatory function of hsa-miR-150-5p in association with the maintenance of stemness in CESCs.</p><p><strong>Methods: </strong>The target mRNAs of hsa-miR-150-5p were predicted and subjected to pathway analysis to identify targets for functional studies. Primary cultured limbal epithelial cells were transfected with hsa-miR-150-5p mimic, inhibitor, or scrambled sequence using Lipofectamine 3000. The transfected cells were analyzed to determine (i) their colony-forming potential; (ii) the expression levels of stem cell (SC) markers/transcription factors (ABCG2, NANOG, OCT4, KLF4, and ΔNp63), the differentiation marker (Cx43), and the hsa-miR-150-5p predicted targets (JARID2, INHBA, AKT3, and CTNNB1) by qPCR; and (iii) the expression levels of ABCG2, p63α, Cx43, JARID2, AKT3, p-AKT3, β-catenin, and active β-catenin by immunofluorescence staining and/or western blotting.</p><p><strong>Results: </strong>The ectopic expression level of hsa-miR-150-5p increased the colony-forming potential (8.29% ± 0.47%, p < 0.001) with the ability to form holoclone-like colonies compared with the control (1.8% ± 0.47%). The mimic-treated cells had higher expression levels of the SC markers but reduced expression levels of Cx43 and the targets of hsa-miR-150-5p that are involved in the Wnt-β-catenin signaling pathway. The expression levels of β-catenin and active β-catenin in the inhibitor-transfected cells were higher than those in the control cells, and the localized nuclear expression indicated the activation of Wnt signaling.</p><p><strong>Conclusions: </strong>Our results indicate a regulatory role for hsa-miR-150-5p in the maintenance of CESCs by inhibiting the Wnt signaling pathway.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":" ","pages":"178-191"},"PeriodicalIF":2.2,"publicationDate":"2022-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f4/1b/mv-v28-178.PMC9491245.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40663805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review: New horizons in retinoblastoma treatment: an updated review article.","authors":"Fatemeh Azimi,&nbsp;Reza Mirshahi,&nbsp;Masood Naseripour","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Retinoblastoma (Rb) is a rare childhood intraocular malignancy with an incidence rate of approximately 9000 children per year worldwide. The management of Rb is inherently complex and depends on several factors. The orders of priorities in the treatment of Rb are saving life, globe salvage and vision salvage. Rarity and the young age at diagnosis impede conducting randomized clinical trials (RCTs) for new therapeutic options, and therefore pre-RCTs studies are needed. This review provides an overview of advances in Rb treatment options, focusing on the emergence of new small molecules to treat Rb. Articles related to the management and treatments of Rb were searched in different databases. Several studies and animal models discussing recent advances in the treatment of Rb were included to have a better grasp of the biological mechanisms of Rb. Over the years, the principles of management and treatment of Rb have changed significantly. Innovations in targeted therapies and molecular biology have led to improved patient and ocular survival. However, there is still a need for further evaluation of the long-term effects of these new treatments.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":" ","pages":"130-146"},"PeriodicalIF":2.2,"publicationDate":"2022-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/04/4d/mv-v28-130.PMC9352364.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33444395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diquafosol ophthalmic solution enhances mucin expression via ERK activation in human conjunctival epithelial cells with hyperosmotic stress.","authors":"Hyun Jung Lee,&nbsp;Soonwon Yang,&nbsp;Eun Jeong Cheon,&nbsp;Soojung Shin,&nbsp;Yong-Soo Byun,&nbsp;Hyun Seung Kim,&nbsp;So-Hyang Chung","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the effect of diquafosol tetrasodium on the expression of secretory and membrane-associated mucins in multi-layered cultures of primary human conjunctival epithelial cells (HCEC) using intracellular extracellular signal regulated kinase (ERK) signaling.</p><p><strong>Methods: </strong>HCECs were treated with hyperosmotic stress (400 mOsm/l) for 24 h after air-liquid interface cell culture followed by treatment with diquafosol. HCECs were stimulated for 1 h with or without PD98059, an ERK inhibitor, then treated with diquafosol for 6 h and 24 h. Mucin 1 (MUC1), mucin 16 (MUC16), and MUC5AC mRNA and protein expression levels were analyzed, and cell viability was detected using an MTT assay. Western blot analysis was used to examine p44/42 MAPK (Erk1/2) and phosphorylated p44/42 MAPK (Erk1/2) expression.</p><p><strong>Results: </strong>Hyperosmotic stressed HCECs demonstrated increased MUC5AC secretion and gene expression when treated with diquafosol. MUC1 mRNA levels increased significantly at 24 h (p<0.01), and expression of MUC16 mRNA levels increased at 6 h and were maintained until 24 h (p<0.05).There was no significant difference in cell viability compared to the control group. Immunostaining results for MUC1, MUC16, and MUC5AC in diquafosol tetrasodium-treated HCECs at 24 h showed more positive cells than in the control group. Phosphorylation of p44/42 MAPK (Erk1/2) signaling molecules significantly increased from 5 min to 60 min (p<0.05). The effects of diquafosol on mucin expressions in hyperosmotic stressed HCECs were significantly inhibited by PD98059, an ERK inhibitor, at 6 h and 24 h.</p><p><strong>Conclusions: </strong>ERK signaling may regulate the expression levels of MUC1, MUC16, and MUC5AC induced by diquafosol in hyperosmotic stressed HCECs.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":" ","pages":"114-123"},"PeriodicalIF":2.2,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/40/bf/mv-v28-114.PMC9352363.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33443920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-exome sequencing identified genes known to be responsible for retinitis pigmentosa in 28 Chinese families.","authors":"Chang Shen,&nbsp;Bing You,&nbsp;Yu-Ning Chen,&nbsp;Yang Li,&nbsp;Wei Li,&nbsp;Wen-Bin Wei","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Retinitis pigmentosa (RP) is a group of highly heterogenetic inherited retinal degeneration diseases. Molecular genetic diagnosis of RP is quite challenging because of the complicated disease-causing mutation spectrum. The aim of this study was to explore the mutation spectrum in Chinese RP patients using next-generation sequencing technology and to explore the genotype-phenotype relationship.</p><p><strong>Method: </strong>In this study, a cost-effective strategy using whole-exome sequencing (WES) was employed to address the genetic diagnosis of 28 RP families in China. One to two patients and zero to two healthy relatives were sequenced in each family. All mutations in WES data that passed through the filtering procedure were searched in relation to 662 gene defects that can cause vision-associated phenotypes (including 89 RP genes in the RetNet Database). All patients visiting the outpatient department received comprehensive ophthalmic examinations.</p><p><strong>Result: </strong>Twenty-five putative pathogenic mutations of 12 genes were detected by WES and were all confirmed by Sanger sequencing in 20 (20/28, 71.4%) families, including the 12 following genes: <i>USH2A</i>, <i>CYP4V2</i>, <i>PRPF31</i>, <i>RHO</i>, <i>RP1</i>, <i>CNGA1</i>, <i>CNGB1</i>, <i>EYS</i>, <i>PRPF3</i>, <i>RP2</i>, <i>RPGR</i>, and <i>TOPORS</i>. Three families were rediagnosed as having Bietti crystalline dystrophy (BCD). <i>USH2A</i> (4/20, 20%) and <i>CYP4V2</i> (3/20, 15%) were found to be the most frequent mutated genes. Seven novel mutations were identified in this research, including mutations in <i>USH2A1, USH2A2</i>, <i>PRPF31</i>, <i>RP2</i>, <i>TOPORS</i>, <i>CNGB1</i>, and <i>RPGR.</i> Phenotype and genotype relationships in the 12 RP genes were analyzed, which revealed later disease onset and more severe visual function defects in <i>CYP4V2</i>.</p><p><strong>Conclusion: </strong>Twenty-five putative pathogenic mutations of 12 genes were detected by WES, and these were all confirmed by Sanger sequencing in 20 (20/28, 71.4%) families, including seven novel mutations. <i>USH2A</i> and <i>CYP4V2</i> were found to be the most frequent genes in this research. Phenotype and genotype relationships were revealed, and the mutation spectrum of RP in Chinese populations was expanded in this research, which may benefit future cutting-edge therapies.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":" ","pages":"96-113"},"PeriodicalIF":2.2,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ef/da/mv-v28-96.PMC9239900.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40491456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive circular RNA expression profiling with associated ceRNA network in orbital venous malformation.","authors":"Jie Yu,&nbsp;Peiwei Chai,&nbsp;Yixiong Zhou,&nbsp;Renbing Jia,&nbsp;Yefei Wang","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Orbital venous malformation (OVM), the most common type of vascular malformation in adults, has a great impact on both visual and cosmetic factors. Circular RNAs (circRNAs) play important roles in various ophthalmological diseases; however, little is known about their function in the pathogenesis of OVM.</p><p><strong>Methods: </strong>We obtained differentially expressed circRNAs, mRNAs, and miRNAs based on RNA sequencing of four OVM tissues and four normal orbital vascular tissues. The circRNA-mRNA coexpression network and circRNA-miRNA-mRNA and competing endogenous RNA (ceRNA) networks were constructed using miRanda software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify the up- and downregulated mRNAs in the circRNA-miRNA-mRNA ceRNA network.</p><p><strong>Results: </strong>Overall, we identified 45 upregulated and 144 downregulated circRNAs, as well as 2,175 upregulated and 1,274 downregulated mRNAs and 156 upregulated and 168 downregulated miRNAs in OVM samples compared with normal orbital vascular tissues. The expression changes of mRNAs and circRNAs detected by quantitative real-time PCR (qRT-PCR) were in line with the RNA-seq results. Then, a ceRNA regulatory network was constructed with these differentially expressed circRNAs, mRNAs, and miRNAs. GO functional analysis revealed that most related biological processes involved extracellular matrix organization, positive regulation of actin nucleation, and so on, which were thought to be involved in the evolution of OVM. KEGG pathway analysis of upregulated mRNAs showed that mucin-type O-glycan biosynthesis, glycosaminoglycan degradation, and the <i>PI3K</i> (Gene ID: 5290; OMIM: 613089)-<i>AKT</i> (Gene ID: 207; OMIM: 114500) signaling pathway were all enriched in OVM samples.</p><p><strong>Conclusions: </strong>Our study provides novel insight into the regulatory mechanism of circRNAs, miRNAs, and mRNAs in the pathogenesis of OVM.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":" ","pages":"83-95"},"PeriodicalIF":2.2,"publicationDate":"2022-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/72/83/mv-v28-83.PMC9239899.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40491455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}