{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:00:38Z","timestamp":1785128438595,"version":"3.55.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Ophthalmol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Traumatic optic nerve and retinal injuries can lead to severe visual impairment, with undetermined underlying molecular mechanism and few reliable molecular biomarkers. This study aims to identify dysregulated genes and signaling pathways potentially involved in these injuries.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We first identified differentially expressed genes (DEGs) and their enriched functions using two time-course gene expression profile datasets after retinal injury of rats. The hub genes were then obtained from DEGs by protein-protein interaction network, and then assessed by receiver operating characteristic curve analysis to check their diagnostic potential in experimental datasets. The potential miRNAs and transcriptional factors (TFs) of hub genes were also investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 312 and 262 DEGs from the two datasets, respectively, with 31 overlapped up DEGs in injury group. These co-up DEGs were highly enriched in immune response-associated pathways and visual system development pathways, including the pivotal JAK-STAT signaling pathway. We then identified 7 hub genes, of which six (\n                      <jats:italic>Aif1<\/jats:italic>\n                      ,\n                      <jats:italic>Cntf<\/jats:italic>\n                      ,\n                      <jats:italic>Gfap<\/jats:italic>\n                      ,\n                      <jats:italic>Lcn2<\/jats:italic>\n                      ,\n                      <jats:italic>Stat1<\/jats:italic>\n                      , and\n                      <jats:italic>Stat3<\/jats:italic>\n                      ) were validated to be associated with diagnostic relevance in experimental datasets. We predicted 54 miRNAs and 25 TFs participating in the regulatory network of hub genes. Finally, we identified that STAT1 and STAT3 were potential transcriptional regulators in hub genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We identified six critical hub genes and potential regulators that may participate in traumatic optic nerve injury, extending the underlying mechanisms of retinal injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fopht.2026.1762890","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T04:26:11Z","timestamp":1785126371000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-genomics data mining identified critical transcription factors and immune response pathways in traumatic optic nerve injury and retinal injury"],"prefix":"10.3389","volume":"6","author":[{"given":"Jinjun","family":"Li","sequence":"first","affiliation":[{"name":"Department of Emergency, The People\u2019s Hospital of Liuyang","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency, The People\u2019s Hospital of Liuyang","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Emergency, The People\u2019s Hospital of Liuyang","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-021-01717-9","article-title":"Traumatic optic neuropathy: a review of current studies","volume":"45","author":"Chen","year":"2022","journal-title":"Neurosurg Rev"},{"key":"B2","doi-asserted-by":"publisher","first-page":"7514","DOI":"10.1038\/s41598-024-54324-1","article-title":"Effects of light perception on visual function recovery in patients with traumatic optic neuropathy","volume":"14","author":"Wang","year":"2024","journal-title":"Sci Rep"},{"key":"B3","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s13024-023-00655-y","article-title":"Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium","volume":"18","author":"Soucy","year":"2023","journal-title":"Mol Neurodegener"},{"key":"B4","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1186\/s12886-024-03404-x","article-title":"One year monitoring of retinal morphologic and functional changes in traumatic optic neuropathy patients","volume":"24","author":"Kim","year":"2024","journal-title":"BMC Ophthalmol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/b978-0-323-03330-5.50032-9","article-title":"Glaucoma in adults-screening, diagnosis, and management: a review","volume":"325","author":"Stein","year":"2021","journal-title":"JAMA"},{"key":"B6","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/s41574-020-00451-4","article-title":"Current understanding of the molecular and cellular pathology of diabetic retinopathy","volume":"17","author":"Antonetti","year":"2021","journal-title":"Nat Rev Endocrinol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.108401","article-title":"Chronobiotic effect of melatonin in experimental optic neuritis","volume":"182","author":"Aranda","year":"2021","journal-title":"Neuropharmacology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.618353","article-title":"Risk factors for non-arteritic anterior ischemic optic neuropathy: a large scale meta-analysis","volume":"8","author":"Liu","year":"2021","journal-title":"Front Med (Lausanne)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-01108-x","article-title":"Nanopore sequencing technology, bioinformatics and applications","volume":"39","author":"Wang","year":"2021","journal-title":"Nat Biotechnol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2025.110494","article-title":"Application of transcriptome sequencing to identify and explore biomarkers in a rat model of optic nerve crush","volume":"258","author":"Yu","year":"2025","journal-title":"Exp Eye Res"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu114","article-title":"Comprehensive analysis of gene expression in human retina and supporting tissues","volume":"23","author":"Li","year":"2014","journal-title":"Hum Mol Genet"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41433-022-02013-6","article-title":"Gene expression profile analyses to identify potential biomarkers for myopia","volume":"37","author":"Ni","year":"2023","journal-title":"Eye (Lond)"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.18240\/ijo.2023.07.03","article-title":"Identification of hub genes for glaucoma: a study based on bioinformatics analysis and experimental verification","volume":"16","author":"Xie","year":"2023","journal-title":"Int J Ophthalmol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0280548","article-title":"Identification of key ferroptosis genes in diabetic retinopathy based on bioinformatics analysis","volume":"18","author":"Huang","year":"2023","journal-title":"PloS One"},{"key":"B15","article-title":"Time course profiling of the retinal transcriptome after optic nerve transection and optic nerve crush","volume":"14","author":"Agudo","year":"2008","journal-title":"Mol Vis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-1047","article-title":"Temporal changes in gene expression after injury in the rat retina","volume":"45","author":"Vazquez-Chona","year":"2004","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B18","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: Elegant Graphics for Data Analysis","author":"Wickham","year":"2016"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics: A J Integr Biol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2262","DOI":"10.3390\/ijms21072262","article-title":"Neuroprotective strategies for retinal ganglion cell degeneration: current status and challenges ahead","volume":"21","author":"Boia","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-023-01373-1","article-title":"Regulated cell death of retinal ganglion cells in glaucoma: molecular insights and therapeutic potentials","volume":"43","author":"Zhao","year":"2023","journal-title":"Cell Mol Neurobiol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.exer.2010.05.016","article-title":"Neurotrophic factor delivery as a protective treatment for glaucoma","volume":"93","author":"Johnson","year":"2011","journal-title":"Exp Eye Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17091584","article-title":"Neuroprotection, growth factors and BDNF-TrkB signalling in retinal degeneration","volume":"17","author":"Kimura","year":"2016","journal-title":"Int J Mol Sci"},{"key":"B25","doi-asserted-by":"publisher","first-page":"987","DOI":"10.3390\/biom11070987","article-title":"Stem cell-based regeneration and restoration for retinal ganglion cell: recent advancements and current challenges","volume":"11","author":"Zhang","year":"2021","journal-title":"Biomolecules"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2022.2103153","article-title":"A review on the application of stem cell secretome in the protection and regeneration of retinal ganglion cells; a clinical prospect in the treatment of optic neuropathies","volume":"47","author":"Sanie-Jahromi","year":"2022","journal-title":"Curr Eye Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"581","DOI":"10.3390\/biom11040581","article-title":"Use of gene therapy in retinal ganglion cell neuroprotection: current concepts and future directions","volume":"11","author":"Rhee","year":"2021","journal-title":"Biomolecules"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2023.03.008","article-title":"Neuroserpin gene therapy inhibits retinal ganglion cell apoptosis and promotes functional preservation in glaucoma","volume":"31","author":"Chitranshi","year":"2023","journal-title":"Mol Ther"},{"key":"B29","doi-asserted-by":"publisher","first-page":"694","DOI":"10.3390\/biology12050694","article-title":"AIF1: function and connection with inflammatory diseases","volume":"12","author":"De Leon-Oliva","year":"2023","journal-title":"Biol (Basel)"},{"key":"B30","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.cellimm.2013.07.008","article-title":"Role of AIF-1 in the regulation of inflammatory activation and diverse disease processes","volume":"284","author":"Zhao","year":"2013","journal-title":"Cell Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132528","article-title":"Microglial physiology: unique stimuli, specialized responses","volume":"27","author":"Ransohoff","year":"2009","journal-title":"Annu Rev Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.125","article-title":"Microglia and macrophages in brain homeostasis and disease","volume":"18","author":"Li","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1103416","article-title":"Microglia activation in central nervous system disorders: a review of recent mechanistic investigations and development efforts","volume":"14","author":"Qin","year":"2023","journal-title":"Front Neurol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-020-01667-9","article-title":"CHI3L2 expression levels are correlated with AIF1, PECAM1, and CALB1 in the brains of Alzheimer's disease patients","volume":"70","author":"Sanfilippo","year":"2020","journal-title":"J Mol Neurosci"},{"key":"B35","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/s0165-5728(99)00222-2","article-title":"Allograft-inflammatory-factor-1 is upregulated in microglial cells in human cerebral infarctions","volume":"104","author":"Postler","year":"2000","journal-title":"J Neuroimmunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/s0165-5728(01)00375-7","article-title":"AIF-1 expression defines a proliferating and alert microglial\/macrophage phenotype following spinal cord injury in rats","volume":"119","author":"Schwab","year":"2001","journal-title":"J Neuroimmunol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1146\/annurev-vision-091517-034425","article-title":"Microglia in the retina: roles in development, maturity, and disease","volume":"4","author":"Silverman","year":"2018","journal-title":"Annu Rev Vis Sci"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23475","article-title":"Microglia mediate non-cell-autonomous cell death of retinal ganglion cells","volume":"66","author":"Takeda","year":"2018","journal-title":"Glia"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01975","article-title":"Microglia in retinal degeneration","volume":"10","author":"Rashid","year":"2019","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302791","article-title":"AAV-mediated expression of CNTF promotes long-term survival and regeneration of adult rat retinal ganglion cells","volume":"13","author":"Leaver","year":"2006","journal-title":"Gene Ther"},{"key":"B41","doi-asserted-by":"publisher","first-page":"025001","DOI":"10.1088\/1748-605x\/ad1bae","article-title":"Ciliary neurotrophic factor mediated growth of retinal ganglion cell axons on PGS\/PCL scaffolds","volume":"19","author":"Behtaj","year":"2024","journal-title":"BioMed Mater"},{"key":"B42","doi-asserted-by":"publisher","first-page":"7037","DOI":"10.1038\/s41467-022-34443-x","article-title":"Ciliary neurotrophic factor-mediated neuroprotection involves enhanced glycolysis and anabolism in degenerating mouse retinas","volume":"13","author":"Do Rhee","year":"2022","journal-title":"Nat Commun"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0209733","article-title":"Application of CNTF or FGF-2 increases the number of M2-like macrophages after optic nerve injury in adult Rana pipiens","volume":"14","author":"Blanco","year":"2019","journal-title":"PloS One"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2020.7039","article-title":"Traumatic optic nerve injury elevates plasma biomarkers of traumatic brain injury in a porcine model","volume":"38","author":"Bramblett","year":"2021","journal-title":"J Neurotrauma"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-015-3127-7","article-title":"Elevated vitreous body glial fibrillary acidic protein in retinal diseases","volume":"253","author":"Junemann","year":"2015","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24500","article-title":"Change in phospholipid species of retinal layer in traumatic optic neuropathy model","volume":"98","author":"Hirahara","year":"2020","journal-title":"J Neurosci Res"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112002","article-title":"Lipocalin-2: structure, function, distribution and role in metabolic disorders","volume":"142","author":"Jaberi","year":"2021","journal-title":"BioMed Pharmacother"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13653","article-title":"Lipocalin 2 regulates iron homeostasis, neuroinflammation, and insulin resistance in the brains of patients with dementia: evidence from the current literature","volume":"27","author":"Lim","year":"2021","journal-title":"CNS Neurosci Ther"},{"key":"B49","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1615\/critrevimmunol.2015012127","article-title":"Lipocalin-2 in the inflammatory activation of brain astrocytes","volume":"35","author":"Lee","year":"2015","journal-title":"Crit Rev Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1358719","article-title":"The interaction of lipocalin-2 and astrocytes in neuroinflammation: mechanisms and therapeutic application","volume":"15","author":"Tan","year":"2024","journal-title":"Front Immunol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/s12974-019-1556-7","article-title":"Lipocalin-2 may produce damaging effect after cerebral ischemia by inducing astrocytes classical activation","volume":"16","author":"Zhao","year":"2019","journal-title":"J Neuroinflamm"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-021-02530-7","article-title":"Lipocalin 2 as a putative modulator of local inflammatory processes in the spinal cord and component of organ cross talk after spinal cord injury","volume":"58","author":"Behrens","year":"2021","journal-title":"Mol Neurobiol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.3390\/antiox10111657","article-title":"Role of lipocalin-2 in amyloid-beta oligomer-induced mouse model of Alzheimer's disease","volume":"10","author":"Kang","year":"2021","journal-title":"Antioxid (Basel)"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-022-01333-5","article-title":"Lipocalin-2 is a key regulator of neuroinflammation in secondary traumatic and ischemic brain injury","volume":"20","author":"Kim","year":"2023","journal-title":"Neurotherapeutics"},{"key":"B55","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.clim.2016.09.014","article-title":"Role of the JAK\/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases","volume":"189","author":"Yan","year":"2018","journal-title":"Clin Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18-25700","article-title":"Early optic nerve head glial proliferation and Jak-Stat pathway activation in chronic experimental glaucoma","volume":"60","author":"Lozano","year":"2019","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1276445","article-title":"Regulation of the JAK\/STAT signaling pathway in spinal cord injury: an updated review","volume":"14","author":"Guo","year":"2023","journal-title":"Front Immunol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1254\/jpssuppl.wcp2018.0_po3-10-11","article-title":"Ginkgo biloba extract inhibits astrocytic lipocalin-2 expression and alleviates neuroinflammatory injury via the JAK2\/STAT3 pathway after ischemic brain stroke","volume":"9","author":"Zhang","year":"2018","journal-title":"Front Pharmacol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1186\/s12974-021-02312-x","article-title":"Photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2\/JAK2-STAT3 crosstalk after spinal cord injury in male rats","volume":"18","author":"Wang","year":"2021","journal-title":"J Neuroinflamm"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.3898-13.2014","article-title":"Jak\/Stat signaling stimulates zebrafish optic nerve regeneration and overcomes the inhibitory actions of Socs3 and Sfpq","volume":"34","author":"Elsaeidi","year":"2014","journal-title":"J Neurosci"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1242\/dev.199694","article-title":"Retinal ganglion cell survival after severe optic nerve injury is modulated by crosstalk between Jak\/Stat signaling and innate immune responses in the zebrafish retina","volume":"149","author":"Chen","year":"2022","journal-title":"Development"}],"container-title":["Frontiers in Ophthalmology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fopht.2026.1762890\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T04:26:13Z","timestamp":1785126373000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fopht.2026.1762890\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":61,"alternative-id":["10.3389\/fopht.2026.1762890"],"URL":"https:\/\/doi.org\/10.3389\/fopht.2026.1762890","relation":{},"ISSN":["2674-0826"],"issn-type":[{"value":"2674-0826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]},"article-number":"1762890"}}