{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:28:24Z","timestamp":1785803304072,"version":"3.56.0"},"reference-count":104,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Central South University School-Enterprise Joint Innovation Project","award":["2021XQLH084"],"award-info":[{"award-number":["2021XQLH084"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glaucoma is a leading cause of permanent blindness, affecting 80 million people worldwide. Recent studies have emphasized the importance of neuroinflammation in the early stages of glaucoma, involving immune and glial cells. To investigate this further, we used the GSE27276 dataset from the GEO (Gene Expression Omnibus) database and neuroinflammation genes from the GeneCards database to identify differentially expressed neuroinflammation-related genes associated with primary open-angle glaucoma (POAG). Subsequently, these genes were submitted to Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes for pathway enrichment analyses. Hub genes were picked out through protein-protein interaction networks and further validated using the external datasets (GSE13534 and GSE9944) and real-time PCR analysis. The gene\u2013miRNA regulatory network, receiver operating characteristic (ROC) curve, genome-wide association study (GWAS), and regional expression analysis were performed to further validate the involvement of hub genes in glaucoma. A total of 179 differentially expressed genes were identified, comprising 60 upregulated and 119 downregulated genes. Among them, 18 differentially expressed neuroinflammation\u2013related genes were found to overlap between the differentially expressed genes and neuroinflammation\u2013related genes, with six genes (SERPINA3, LCN2, MMP3, S100A9, IL1RN, and HP) identified as potential hub genes. These genes were related to the IL-17 signaling pathway and tyrosine metabolism. The gene\u2013miRNA regulatory network showed that these hub genes were regulated by 118 miRNAs. Notably, GWAS data analysis successfully identified significant single nucleotide polymorphisms (SNPs) corresponding to these six hub genes. ROC curve analysis indicated that our genes showed significant accuracy in POAG. The expression of these genes was further confirmed in microglia, M\u00fcller cells, astrocytes, and retinal ganglion cells in the Spectacle database. Moreover, three hub genes, SERPINA3, IL1R1, and LCN2, were validated as potential diagnostic biomarkers for high-risk glaucoma patients, showing increased expression in the OGD\/R-induced glaucoma model. This study suggests that the identified hub genes may influence the development of POAG by regulation of neuroinflammation, and it may offer novel insights into the management of POAG.<\/jats:p>","DOI":"10.3390\/ijms25158193","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T14:39:08Z","timestamp":1722004748000},"page":"8193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Integrated Bioinformatics-Based Identification and Validation of Neuroinflammation-Related Hub Genes in Primary Open-Angle Glaucoma"],"prefix":"10.3390","volume":"25","author":[{"given":"Zakir","family":"Ullah","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4627-3161","authenticated-orcid":false,"given":"Yuanyuan","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jufang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wu, Y., Szymanska, M., Hu, Y., Fazal, M.I., Jiang, N., Yetisen, A.K., and Cordeiro, M.F. (2022). Measures of disease activity in glaucoma. Biosens. Bioelectron., 196.","DOI":"10.1016\/j.bios.2021.113700"},{"key":"ref_2","first-page":"e11686","article-title":"Epidemiology of Glaucoma: The Past, Present, and Predictions for the Future","volume":"12","author":"Allison","year":"2020","journal-title":"Cureus"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13762","DOI":"10.1038\/s41598-021-92971-w","article-title":"Prevalence of primary open angle glaucoma in the last 20 years: A meta-analysis and systematic review","volume":"11","author":"Zhang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.3390\/encyclopedia2040124","article-title":"Pathogenesis of Glaucoma","volume":"2","author":"Macanian","year":"2022","journal-title":"Encyclopedia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.exer.2017.02.014","article-title":"Neuroinflammation in glaucoma: A new opportunity","volume":"157","author":"Williams","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100916","DOI":"10.1016\/j.preteyeres.2020.100916","article-title":"Inflammation in Glaucoma: From the back to the front of the eye, and beyond","volume":"83","author":"Baudouin","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_7","first-page":"225","article-title":"The Diagnosis and Treatment of Glaucoma","volume":"117","author":"Schuster","year":"2020","journal-title":"Dtsch. Arzteblatt Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/aos.14861","article-title":"Aqueous eye drops containing drug\/cyclodextrin nanoparticles deliver therapeutic drug concentrations to both anterior and posterior segment","volume":"100","author":"Loftsson","year":"2022","journal-title":"Acta Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"114781","DOI":"10.1016\/j.addr.2023.114781","article-title":"Gene therapy strategies for glaucoma from IOP reduction to retinal neuroprotection: Progress towards non-viral systems","volume":"196","author":"Hakim","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Tao, Y., Zhang, Q., Meng, M., and Huang, J. (2023). A bibliometric analysis of the application of stem cells in glaucoma research from 1999 to 2022. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1081898"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Choi, S., Choi, S.-H., Bastola, T., Park, Y., Oh, J., Kim, K.-Y., Hwang, S., Miller, Y.I., and Ju, W.-K. (2024). AIBP: A New Safeguard against Glaucomatous Neuroinflammation. Cells, 13.","DOI":"10.3390\/cells13020198"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4581909","DOI":"10.1155\/2021\/4581909","article-title":"Neuroinflammatory Mechanisms of Mitochondrial Dysfunction and Neurodegeneration in Glaucoma","volume":"2021","author":"Duarte","year":"2021","journal-title":"J. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.coph.2012.09.013","article-title":"Immune regulation toward immunomodulation for neuroprotection in glaucoma","volume":"13","author":"Tezel","year":"2013","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ramirez, A.I., de Hoz, R., Salobrar-Garcia, E., Salazar, J.J., Rojas, B., Ajoy, D., L\u00f3pez-Cuenca, I., Rojas, P., Trivi\u00f1o, A., and Ram\u00edrez, J.M. (2017). The Role of Microglia in Retinal Neurodegeneration: Alzheimer\u2019s Disease, Parkinson, and Glaucoma. Front. Aging Neurosci., 9.","DOI":"10.3389\/fnagi.2017.00214"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/jnc.14070","article-title":"Involvement of microglia in early axoglial alterations of the optic nerve induced by experimental glaucoma","volume":"142","author":"Bordone","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s10792-017-0795-9","article-title":"Pathophysiology of primary open-angle glaucoma from a neuroinflammatory and neurotoxicity perspective: A review of the literature","volume":"39","author":"Evangelho","year":"2019","journal-title":"Int. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"391","DOI":"10.4103\/1673-5374.245465","article-title":"Neuroinflammation as a target for glaucoma therapy","volume":"14","author":"Adornetto","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Albarral, J.A., Salazar, J.J., De Hoz, R., Marco, E.M., Mart\u00edn-S\u00e1nchez, B., Flores-Salguero, E., Salobrar-Garc\u00eda, E., L\u00f3pez-Cuenca, I., Barrios-Sabador, V., and Avil\u00e9s-Trigueros, M. (2021). Retinal Molecular Changes Are Associated with Neuroinflammation and Loss of RGCs in an Experimental Model of Glaucoma. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22042066"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhao, X., Sun, R., Luo, X., Wang, F., and Sun, X. (2021). The Interaction Between Microglia and Macroglia in Glaucoma. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.610788"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Vernazza, S., Tirendi, S., Bassi, A.M., Traverso, C.E., and Sacc\u00e0, S.C. (2020). Neuroinflammation in Primary Open-Angle Glaucoma. J. Clin. Med., 9.","DOI":"10.3390\/jcm9103172"},{"key":"ref_21","first-page":"656","article-title":"Research progress on human genes involved in the pathogenesis of glaucoma (Review)","volume":"18","author":"Wang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4900","DOI":"10.1111\/jcmm.15197","article-title":"MicroRNA regulatory networks in the pathogenesis of sarcopenia","volume":"24","author":"Yin","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e14472","DOI":"10.1111\/cns.14472","article-title":"SERPINA3: A novel inflammatory biomarker associated with cerebral small vessel disease burden in ischemic stroke","volume":"30","author":"Hu","year":"2023","journal-title":"CNS Neurosci. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1038\/s41467-018-05681-9","article-title":"Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma","volume":"9","author":"Chen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3778","DOI":"10.1007\/s12035-022-02817-3","article-title":"Serpin Signatures in Prion and Alzheimer\u2019s Diseases","volume":"59","author":"Zattoni","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1080\/1061186X.2019.1693576","article-title":"Serpina3n: Potential drug and challenges, mini review","volume":"28","author":"Aslam","year":"2020","journal-title":"J. Drug Target."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s40478-014-0093-y","article-title":"Integrated multi-cohort transcriptional meta-analysis of neurodegenerative diseases","volume":"2","author":"Li","year":"2014","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1002\/pmic.201600047","article-title":"Key players in neurodegenerative disorders in focus\u2014New insights into the proteomic profile of Alzheimer\u2019s disease, schizophrenia, ALS, and multiple sclerosis\u201424th HUPO BPP Workshop: September 29, 2015, Vancouver, Canada","volume":"16","author":"Park","year":"2016","journal-title":"Proteomics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1002\/iid3.515","article-title":"Highly expressed of SERPINA3 indicated poor prognosis and involved in immune suppression in glioma","volume":"9","author":"Yuan","year":"2021","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/s12974-023-02840-8","article-title":"Astrocyte-derived SerpinA3N promotes neuroinflammation and epileptic seizures by activating the NF-\u03baB signaling pathway in mice with temporal lobe epilepsy","volume":"20","author":"Liu","year":"2023","journal-title":"J. Neuroinflammation"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yamanaka, G., Ishida, Y., Kanou, K., Suzuki, S., Watanabe, Y., Takamatsu, T., Morichi, S., Go, S., Oana, S., and Yamazaki, T. (2021). Towards a Treatment for Neuroinflammation in Epilepsy: Interleukin-1 Receptor Antagonist, Anakinra, as a Potential Treatment in Intractable Epilepsy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126282"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00401-013-1208-4","article-title":"The role of pro-inflammatory S100A9 in Alzheimer\u2019s disease amyloid-neuroinflammatory cascade","volume":"127","author":"Wang","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1186\/s12974-018-1210-9","article-title":"Co-aggregation of pro-inflammatory S100A9 with \u03b1-synuclein in Parkinson\u2019s disease: Ex vivo and in vitro studies","volume":"15","author":"Horvath","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/imm.13722","article-title":"Roles of S100A8, S100A9 and S100A12 in infection, inflammation and immunity","volume":"171","author":"Xia","year":"2023","journal-title":"Immunology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1080\/09273948.2018.1538461","article-title":"Circulating S100A8\/A9 Levels Reflect Intraocular Inflammation in Uveitis Patients","volume":"28","author":"Wang","year":"2020","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jtos.2013.10.001","article-title":"S100A Proteins as Molecular Targets in the Ocular Surface Inflammatory Diseases","volume":"12","author":"Tong","year":"2014","journal-title":"Ocul. Surf."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Singh, P., and Ali, S.A. (2022). Multifunctional Role of S100 Protein Family in the Immune System: An Update. Cells, 11.","DOI":"10.3390\/cells11152274"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7385","DOI":"10.1167\/iovs.10-6532","article-title":"Proteomic Profiling of Inflammatory Signaling Molecules in the Tears of Patients on Chronic Glaucoma Medication","volume":"52","author":"Wong","year":"2011","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.pneurobio.2015.06.005","article-title":"From the periphery to the brain: Lipocalin-2, a friend or foe?","volume":"131","author":"Ferreira","year":"2015","journal-title":"Prog. Neurobiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"763","DOI":"10.3233\/JAD-160330","article-title":"Neutrophil Gelatinase-Associated Lipocalin and its Receptors in Alzheimer\u2019s Disease (AD) Brain Regions: Differential Findings in AD with and without Depression","volume":"55","author":"Dekens","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/s41467-020-14373-2","article-title":"Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia","volume":"11","author":"Llorens","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5608","DOI":"10.1523\/JNEUROSCI.4261-15.2016","article-title":"Pathogenic Upregulation of Glial Lipocalin-2 in the Parkinsonian Dopaminergic System","volume":"36","author":"Kim","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e191","DOI":"10.1212\/NXI.0000000000000191","article-title":"Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination","volume":"3","author":"Elliott","year":"2016","journal-title":"Neurol. Neuroimmunol. Neuroinflammation"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1038\/cdd.2014.68","article-title":"Lipocalin 2 modulates the cellular response to amyloid beta","volume":"21","author":"Mesquita","year":"2014","journal-title":"Cell Death Differ."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"28736","DOI":"10.1038\/srep28736","article-title":"Transcriptome profiling of the rat retina after optic nerve transection","volume":"6","author":"Yasuda","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1167\/iovs.17-22438","article-title":"Early Gene Expression Profile in Retinal Ganglion Cell Layer After Optic Nerve Crush in Mice","volume":"59","author":"Ueno","year":"2018","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Yoneshige, A., Hagiyama, M., Takashima, Y., Ueno, S., Inoue, T., Kimura, R., Koriyama, Y., and Ito, A. (2021). Elevated Hydrostatic Pressure Causes Retinal Degeneration Through Upregulating Lipocalin-2. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.664327"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Tokito, A., and Jougasaki, M. (2016). Matrix Metalloproteinases in Non-Neoplastic Disorders. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071178"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1093\/hmg\/ddx028","article-title":"Therapeutic potential of AAV-mediated MMP-3 secretion from corneal endothelium in treating glaucoma","volume":"26","author":"Crosbie","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1089\/jop.2019.0146","article-title":"Matrix Metalloproteinases and Glaucoma Treatment","volume":"36","author":"Weinreb","year":"2020","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"eadf6537","DOI":"10.1126\/sciadv.adf6537","article-title":"Matrix metalloproteinase-3 (MMP-3)\u2013mediated gene therapy for glaucoma","volume":"9","author":"Delaney","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/prd.12083","article-title":"Basic biology and role of interleukin-17 in immunity and inflammation","volume":"69","author":"Zenobia","year":"2015","journal-title":"Periodontol. 2000"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Chen, J., Liu, X., and Zhong, Y. (2020). Interleukin-17A: The Key Cytokine in Neurodegenerative Diseases. Front. Aging Neurosci., 12.","DOI":"10.3389\/fnagi.2020.566922"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Milovanovic, J., Arsenijevic, A., Stojanovic, B., Kanjevac, T., Arsenijevic, D., Radosavljevic, G., Milovanovic, M., and Arsenijevic, N. (2020). Interleukin-17 in Chronic Inflammatory Neurological Diseases. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00947"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e22945","DOI":"10.1096\/fj.202202056RR","article-title":"Interleukin-17A modulates retinal inflammation by regulating microglial activation via the p38 MAPK pathway in experimental glaucoma neuropathy","volume":"37","author":"Chen","year":"2023","journal-title":"FASEB J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40035-020-00221-2","article-title":"Neuroinflammation in neurodegenerative disorders: The roles of microglia and astrocytes","volume":"9","author":"Kwon","year":"2020","journal-title":"Transl. Neurodegener."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Scimone, C., Granata, F., Longo, M., Mormina, E., Turiaco, C., Caragliano, A.A., Donato, L., Sidoti, A., and D\u2019Angelo, R. (2020). Germline Mutation Enrichment in Pathways Controlling Endothelial Cell Homeostasis in Patients with Brain Arteriovenous Malformation: Implication for Molecular Diagnosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124321"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Zhong, H., and Sun, X. (2022). Contribution of Interleukin-17A to Retinal Degenerative Diseases. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.847937"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Dobrzycka, M., Sulewska, A., Biecek, P., Charkiewicz, R., Karabowicz, P., Charkiewicz, A., Golaszewska, K., Milewska, P., Michalska-Falkowska, A., and Nowak, K. (2023). miRNA Studies in Glaucoma: A Comprehensive Review of Current Knowledge and Future Perspectives. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914699"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/bfgp\/elaa020","article-title":"An update: Mechanisms of microRNA in primary open-angle glaucoma","volume":"20","author":"Wang","year":"2021","journal-title":"Brief. Funct. Genomics"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Kondkar, A.A., Azad, T.A., Sultan, T., Radhakrishnan, R., Osman, E.A., Almobarak, F.A., Lobo, G.P., and Al-Obeidan, S.A. (2022). Polymorphism rs3742330 in microRNA Biogenesis Gene DICER1 Is Associated with Pseudoexfoliation Glaucoma in Saudi Cohort. Genes, 13.","DOI":"10.3390\/genes13030489"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.2147\/OPTH.S254504","article-title":"Differential miRNA Expression: Signature for Glaucoma in Pseudoexfoliation","volume":"14","author":"Rao","year":"2020","journal-title":"Clin. Ophthalmol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Kathirvel, K., Fan, X., Haribalaganesh, R., Bharanidharan, D., Sharmila, R., Krishnadas, R., Muthukkaruppan, V., Willoughby, C.E., and Senthilkumari, S. (2023). Small RNA Sequencing Reveals a Distinct MicroRNA Signature between Glucocorticoid Responder and Glucocorticoid Non-Responder Primary Human Trabecular Meshwork Cells after Dexamethasone Treatment. Genes, 14.","DOI":"10.1101\/2023.06.19.545545"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zingale, V.D., Gugliandolo, A., and Mazzon, E. (2021). MiR-155: An Important Regulator of Neuroinflammation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010090"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"23264","DOI":"10.1074\/jbc.M115.646950","article-title":"Single and Compound Knock-outs of MicroRNA (miRNA)-155 and Its Angiogenic Gene Target CCN1 in Mice Alter Vascular and Neovascular Growth in the Retina via Resident Microglia","volume":"290","author":"Yan","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12950-017-0162-7","article-title":"Knockdown of miR-155 protects microglia against LPS-induced inflammatory injury via targeting RACK1: A novel research for intracranial infection","volume":"14","author":"Yin","year":"2017","journal-title":"J. Inflamm."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/jcbfm.2014.207","article-title":"Brain Endothelial miR-146a Negatively Modulates T-Cell Adhesion through Repressing Multiple Targets to Inhibit NF-\u03baB Activation","volume":"35","author":"Wu","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.bbi.2019.01.020","article-title":"MicroRNA-146a protects against cognitive decline induced by surgical trauma by suppressing hippocampal neuroinflammation in mice","volume":"78","author":"Chen","year":"2019","journal-title":"Brain. Behav. Immun."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Ishikawa, M., Izumi, Y., Sato, K., Sato, T., Zorumski, C.F., Kunikata, H., and Nakazawa, T. (2023). Glaucoma and microglia-induced neuroinflammation. Front. Ophthalmol., 3.","DOI":"10.3389\/fopht.2023.1132011"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"100998","DOI":"10.1016\/j.preteyeres.2021.100998","article-title":"Molecular regulation of neuroinflammation in glaucoma: Current knowledge and the ongoing search for new treatment targets","volume":"87","author":"Tezel","year":"2022","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1172\/JCI44646","article-title":"Molecular clustering identifies complement and endothelin induction as early events in a mouse model of glaucoma","volume":"121","author":"Howell","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1167\/tvst.10.1.22","article-title":"When Is a Control Not a Control? Reactive Microglia Occur Throughout the Control Contralateral Pathway of Retinal Ganglion Cell Projections in Experimental Glaucoma","volume":"10","author":"Tribble","year":"2021","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s40478-022-01427-3","article-title":"Widespread retina and optic nerve neuroinflammation in enucleated eyes from glaucoma patients","volume":"10","author":"Rutigliani","year":"2022","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13024-016-0091-6","article-title":"Inhibition of the classical pathway of the complement cascade prevents early dendritic and synaptic degeneration in glaucoma","volume":"11","author":"Williams","year":"2016","journal-title":"Mol. Neurodegener."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.brainresbull.2018.09.014","article-title":"S100A8\/A9 induces microglia activation and promotes the apoptosis of oligodendrocyte precursor cells by activating the NF-\u03baB signaling pathway","volume":"143","author":"Wu","year":"2018","journal-title":"Brain Res. Bull."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1007\/s12031-023-02168-1","article-title":"Effect of Proinflammatory S100A9 Protein on Migration and Proliferation of Microglial Cells","volume":"73","author":"Bai","year":"2023","journal-title":"J. Mol. Neurosci."},{"key":"ref_77","unstructured":"Matt, S.M. (2018). Epigenetic Regulation of Neuroinflammation in the Aged Mouse Brain, University of Illinois."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"164","DOI":"10.31117\/neuroscirn.v6i1.164","article-title":"Interleukin 1 receptor antagonist and neurodegenerative diseases: The future treatment strategy","volume":"6","author":"Retinasamy","year":"2023","journal-title":"Neurosci. Res. Notes"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1021\/acschemneuro.3c00650","article-title":"The Surprising Nonlinear Effects of S100A9 Proteins in the Retina","volume":"15","author":"Naaman","year":"2024","journal-title":"ACS Chem. Neurosci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.imlet.2023.02.008","article-title":"Proinflammatory S100A9 stimulates TLR4\/NF-\u03baB signaling pathways causing enhanced phagocytic capacity of microglial cells","volume":"255","author":"Zhang","year":"2023","journal-title":"Immunol. Lett."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"109165","DOI":"10.1016\/j.isci.2024.109165","article-title":"S100A9 aggravates early brain injury after subarachnoid hemorrhage via inducing neuroinflammation and inflammasome activation","volume":"27","author":"Wang","year":"2024","journal-title":"iScience"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s10753-020-01334-6","article-title":"S100A9 Upregulation Contributes to Learning and Memory Impairments by Promoting Microglia M1 Polarization in Sepsis Survivor Mice","volume":"44","author":"Liao","year":"2021","journal-title":"Inflammation"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Shi, M., Cao, Y., Zhang, X., Zhang, Y., Zhu, Y., Liu, L., Mi, L., Liu, X., Zhou, Y., and Li, S. (2023). Inhibition of S100a8\/A9 Ameliorates Neuroinflammation by Blocking NET Formation Via AMPK\/Nrf2\/HO-1 Pathway after Traumatic Brain Injury in Mice, SSRN.","DOI":"10.2139\/ssrn.4364383"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"291","DOI":"10.3892\/etm.2022.11220","article-title":"S100A9 blockade improves the functional recovery after spinal cord injury via mediating neutrophil infiltration","volume":"23","author":"Sun","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Rolle, T., Ponzetto, A., and Malinverni, L. (2021). The Role of Neuroinflammation in Glaucoma: An Update on Molecular Mechanisms and New Therapeutic Options. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.612422"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.bbi.2020.03.033","article-title":"S100A9 plays a pivotal role in a mouse model of herpetic neuralgia via TLR4\/TNF pathway","volume":"88","author":"Silva","year":"2020","journal-title":"Brain. Behav. Immun."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Jing, Y., Yang, D., Fu, Y., Wang, W., Yang, G., Yuan, F., Chen, H., Ding, J., Chen, S., and Tian, H. (2019). Neuroprotective Effects of Serpina3k in Traumatic Brain Injury. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.01215"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4863","DOI":"10.1167\/iovs.14-14023","article-title":"Serine Proteinase Inhibitor SERPINA3K Suppresses Corneal Neovascularization Via Inhibiting Wnt Signaling and VEGF","volume":"55","author":"Zhou","year":"2014","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_89","first-page":"C106","article-title":"Integrative view of serpins in health and disease: The contribution of serpinA3","volume":"320","author":"Bobadilla","year":"2020","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"De Mezer, M., Rogali\u0144ski, J., Przewo\u017any, S., Chojnicki, M., Niepolski, L., Sobieska, M., and Przysta\u0144ska, A. (2023). SERPINA3: Stimulator or Inhibitor of Pathological Changes. Biomedicines, 11.","DOI":"10.3390\/biomedicines11010156"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1038\/s12276-023-01098-7","article-title":"Lipocalin-2: A therapeutic target to overcome neurodegenerative diseases by regulating reactive astrogliosis","volume":"55","author":"Jung","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1080\/15548627.2023.2180202","article-title":"Reduced secretion of LCN2 (lipocalin 2) from reactive astrocytes through autophagic and proteasomal regulation alleviates inflammatory stress and neuronal damage","volume":"19","author":"Jung","year":"2023","journal-title":"Autophagy"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Raeeszadeh-Sarmazdeh, M., Do, L., and Hritz, B. (2020). Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics. Cells, 9.","DOI":"10.3390\/cells9051313"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1.30.1","DOI":"10.1002\/cpbi.5","article-title":"The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses","volume":"54","author":"Stelzer","year":"2016","journal-title":"Curr. Protoc. Bioinforma."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"W367","DOI":"10.1093\/nar\/gkac364","article-title":"GEOexplorer: A webserver for gene expression analysis and visualisation","volume":"50","author":"Hunt","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1016\/j.molp.2023.09.010","article-title":"TBtools-II: A \u201cone for all, all for one\u201d bioinformatics platform for biological big-data mining","volume":"16","author":"Chen","year":"2023","journal-title":"Mol. Plant"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","article-title":"ShinyGO: A graphical gene-set enrichment tool for animals and plants","volume":"36","author":"Ge","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1093\/bib\/bbw114","article-title":"Genome, transcriptome and proteome: The rise of omics data and their integration in biomedical sciences","volume":"19","author":"Manzoni","year":"2018","journal-title":"Brief. Bioinform."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein\u2013protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"W244","DOI":"10.1093\/nar\/gkaa467","article-title":"miRNet 2.0: Network-based visual analytics for miRNA functional analysis and systems biology","volume":"48","author":"Chang","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"108204","DOI":"10.1016\/j.exer.2020.108204","article-title":"Spectacle: An interactive resource for ocular single-cell RNA sequencing data analysis","volume":"200","author":"Voigt","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41598-023-27977-7","article-title":"Identification and validation of oxidative stress and immune-related hub genes in Alzheimer\u2019s disease through bioinformatics analysis","volume":"13","author":"Li","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41418-022-01046-4","article-title":"Pathologically high intraocular pressure disturbs normal iron homeostasis and leads to retinal ganglion cell ferroptosis in glaucoma","volume":"30","author":"Yao","year":"2023","journal-title":"Cell Death Differ."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8193\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:24:42Z","timestamp":1760109882000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,26]]},"references-count":104,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25158193"],"URL":"https:\/\/doi.org\/10.3390\/ijms25158193","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,26]]}}}