{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T23:54:01Z","timestamp":1783122841353,"version":"3.54.6"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005273","name":"Natural Science Foundation of Yunnan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005273","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>To investigate the role of the lamina cribrosa (LC) astrocytes in the autoregulatory capacity of optic nerve head (ONH) vessels and to explore the underlying molecular mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The Oxygen-glucose deprivation\/reperfusion model (OGD\/R) <jats:italic>in vitro<\/jats:italic> was constructed to examine the changes in cell morphology and protein expression in LC astrocytes. LC astrocytes were co-cultured with vascular smooth muscle cells (VSMCs) to detect the role of LC astrocytes in the autoregulatory function of vessels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The partial pressure of oxygen (PO<jats:sub>2<\/jats:sub>) in the supernatant of LC astrocytes was significantly lower following OGD, and this reduction was more pronounced with longer OGD durations. OGD inhibited proliferation and promoted apoptosis in LC astrocytes, with longer OGD durations correlating with decreased proliferation and increased apoptosis. Reoxygenation following 1 h of OGD led to upregulation of GFAP, mTOR, cPLA<jats:sub>2<\/jats:sub> protein expression and supernatant PGE2 concentration in LC astrocytes, an effect that can be attenuated by the mTOR inhibitor. Co-culturing with LC astrocyte resulted in increased expression of MYPT1 protein in VSMCs, and the VSMCs exhibited a relaxed morphology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Under <jats:italic>in vitro<\/jats:italic> OGD\/R conditions, LC astrocyte were activated through the mTOR pathway, leading to increased secretion of PGE<jats:sub>2<\/jats:sub>, which locally regulates the dilation of VSMCs. In conclusion, LC astrocytes may regulate local blood flow in the ONH.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmolb.2025.1636882","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T04:16:02Z","timestamp":1755058562000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Astrocytes from lamina cribrosa are involved in the autoregulatory function of optic nerve head vessels in vitro"],"prefix":"10.3389","volume":"12","author":[{"given":"Xiaoxiao","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangwei","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libo","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1136\/bjo-2022-322254","article-title":"Vascular supply of the optic nerve head: implications for optic disc ischaemia","volume":"107","author":"Arnold","year":"2023","journal-title":"Br. J. Ophthalmol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"117862","DOI":"10.1016\/j.lfs.2020.117862","article-title":"Biochemical analysis of ectonucleotidases on primary rat vascular smooth muscle cells and in silico investigation of their role in vascular diseases","volume":"256","author":"Bertoni","year":"2020","journal-title":"Life Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.3390\/cells10061368","article-title":"Astrocyte networks as therapeutic targets in glaucomatous neurodegeneration","volume":"10","author":"Boal","year":"2021","journal-title":"Cells"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1016\/j.cmet.2021.07.006","article-title":"Astrocyte-neuron metabolic cooperation shapes brain activity","volume":"33","author":"Bonvento","year":"2021","journal-title":"Cell Metab."},{"key":"B5","doi-asserted-by":"publisher","first-page":"C485","DOI":"10.1152\/ajpcell.00161.2012","article-title":"Role of serine-threonine phosphoprotein phosphatases in smooth muscle contractility","volume":"304","author":"Butler","year":"2013","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1523\/JNEUROSCI.4178-07.2008","article-title":"A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function","volume":"28","author":"Cahoy","year":"2008","journal-title":"J. Neurosci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"9765","DOI":"10.3390\/ijms22189765","article-title":"AMPK-mTOR signaling and cellular adaptations in hypoxia","volume":"22","author":"Chun","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1167\/iovs.11-8009","article-title":"Biomechanics of the human posterior sclera: age-and glaucoma-related changes measured using inflation testing","volume":"53","author":"Coudrillier","year":"2012","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.conb.2019.06.004","article-title":"Vascular and neural basis of the BOLD signal","volume":"58","author":"Drew","year":"2019","journal-title":"Curr. Opin. Neurobiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/s41593-020-00783-4","article-title":"Reactive astrocyte nomenclature, definitions, and future directions","volume":"24","author":"Escartin","year":"2021","journal-title":"Nat. Neurosci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"105080","DOI":"10.1016\/j.neuint.2021.105080","article-title":"A1\/A2 astrocytes in central nervous system injuries and diseases: angels or devils?","volume":"148","author":"Fan","year":"2021","journal-title":"Neurochem. Int."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3449","DOI":"10.1007\/s10571-023-01397-7","article-title":"Single-cell RNA-sequencing in astrocyte development, heterogeneity, and disease","volume":"43","author":"Gao","year":"2023","journal-title":"Cell Mol. Neurobiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"624983","DOI":"10.3389\/fneur.2021.624983","article-title":"Glial cells in glaucoma: friends, foes, and potential therapeutic targets","volume":"12","author":"Garc\u00eda-Berm\u00fadez","year":"2021","journal-title":"Front. Neurol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.it.2020.07.007","article-title":"The role of astrocytes in CNS inflammation","volume":"41","author":"Giovannoni","year":"2020","journal-title":"Trends Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"118978","DOI":"10.1016\/j.lfs.2020.118978","article-title":"Regulation of autophagy by controlling Erk1\/2 and mTOR for platelet-derived growth factor-BB-mediated vascular smooth muscle cell phenotype shift","volume":"267","author":"Han","year":"2021","journal-title":"Life Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"R326","DOI":"10.1016\/j.cub.2021.01.056","article-title":"Astrocytes","volume":"31","author":"Hasel","year":"2021","journal-title":"Curr. Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1186\/s13578-022-00932-1","article-title":"Astrocyte derived TSP2 contributes to synaptic alteration and visual dysfunction in retinal ischemia\/reperfusion injury","volume":"12","author":"Hu","year":"2022","journal-title":"Cell Biosci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s13045-019-0754-1","article-title":"Targeting mTOR for cancer therapy","volume":"12","author":"Hua","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1038\/s41573-022-00390-x","article-title":"Function and therapeutic value of astrocytes in neurological diseases","volume":"21","author":"Lee","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"B20","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.bbrc.2018.01.016","article-title":"Blockage of cytosolic phospholipase A2 alpha sensitizes aggressive breast cancer to doxorubicin through suppressing ERK and mTOR kinases","volume":"496","author":"Li","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B21","doi-asserted-by":"publisher","first-page":"664","DOI":"10.14336\/AD.2018.0720","article-title":"Reactive astrocytes in neurodegenerative diseases","volume":"10","author":"Li","year":"2019","journal-title":"Aging Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1167\/iovs.61.11.14","article-title":"Pressure-induced changes in astrocyte GFAP, actin, and nuclear morphology in mouse optic nerve","volume":"61","author":"Ling","year":"2020","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/s41580-019-0199-y","article-title":"mTOR at the nexus of nutrition, growth, ageing and disease","volume":"21","author":"Liu","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2582","DOI":"10.4103\/1673-5374.339470","article-title":"Astrocyte polarization in glaucoma: a new opportunity","volume":"17","author":"Liu","year":"2022","journal-title":"Neural Regen. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"108103","DOI":"10.1016\/j.exer.2020.108103","article-title":"Isolation and characterization of human optic nerve head astrocytes and Lamina cribrosa cells","volume":"197","author":"Lopez","year":"2020","journal-title":"Exp. Eye Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1173200","DOI":"10.3389\/fncel.2023.1173200","article-title":"Reactive astrogliosis in the era of single-cell transcriptomics","volume":"17","author":"Matusova","year":"2023","journal-title":"Front. Cell Neurosci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.semcancer.2019.07.003","article-title":"mTOR: role in cancer, metastasis and drug resistance","volume":"59","author":"Murugan","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"3276","DOI":"10.1523\/JNEUROSCI.4707-08.2009","article-title":"Uniquely hominid features of adult human astrocytes","volume":"29","author":"Oberheim","year":"2009","journal-title":"J. Neurosci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2158","DOI":"10.1111\/j.1582-4934.2008.00536.x","article-title":"The potential role of MLC phosphatase and MAPK signalling in the pathogenesis of vascular dysfunction in heart failure","volume":"12","author":"Ogut","year":"2008","journal-title":"J. Cell Mol. Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.3390\/cells13121046","article-title":"Effect of bromfenac on reducing neuroinflammation in an ischemia-reperfusion glaucoma model","volume":"13","author":"Oh","year":"2024","journal-title":"Cells"},{"key":"B31","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.ydbio.2021.07.007","article-title":"Seeing stars: development and function of retinal astrocytes","volume":"478","author":"Paisley","year":"2021","journal-title":"Dev. Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1002\/glia.20181","article-title":"Astrocytes in cerebral ischemic injury: morphological and general considerations","volume":"50","author":"Panickar","year":"2005","journal-title":"Glia"},{"key":"B33","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.3390\/ijms23052646","article-title":"Key role of astrocytes in postnatal brain and retinal angiogenesis","volume":"23","author":"Puebla","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s13024-021-00428-5","article-title":"Mammalian\/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration","volume":"16","author":"Querfurth","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"B35","doi-asserted-by":"publisher","first-page":"105115","DOI":"10.1016\/j.phrs.2020.105115","article-title":"Regulation of blood-retinal barrier cell-junctions in diabetic retinopathy","volume":"161","author":"Rudraraju","year":"2020","journal-title":"Pharmacol. Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1097\/ICU.0000000000000829","article-title":"Glaucoma and biomechanics","volume":"33","author":"Safa","year":"2022","journal-title":"Curr. Opin. Ophthalmol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"996","DOI":"10.3390\/ijms20040996","article-title":"Aberrant calcium signals in reactive astrocytes: a key process in neurological disorders","volume":"20","author":"Shigetomi","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.jphs.2020.12.009","article-title":"Potential roles of astrocytes and m\u00fcller cells in the pathogenesis of glaucoma","volume":"145","author":"Shinozaki","year":"2021","journal-title":"J. Pharmacol. Sci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1002\/(sici)1098-1136(199908)27:2<110::aid-glia2>3.0.co;2-c","article-title":"Cytosolic phospholipase A2 is induced in reactive glia following different forms of neurodegeneration","volume":"27","author":"Stephenson","year":"1999","journal-title":"Glia"},{"key":"B40","doi-asserted-by":"publisher","first-page":"8068","DOI":"10.3390\/ijms23158068","article-title":"Remodeling of the lamina cribrosa: mechanisms and potential therapeutic approaches for glaucoma","volume":"23","author":"Strickland","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B41","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1385\/MN:31:1-3:027","article-title":"Phospholipase A2 in astrocytes: responses to oxidative stress, inflammation, and G protein-coupled receptor agonists","volume":"31","author":"Sun","year":"2005","journal-title":"Mol. Neurobiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1002\/glia.22507","article-title":"Reversible reactivity by optic nerve astrocytes","volume":"61","author":"Sun","year":"2013","journal-title":"Glia"},{"key":"B43","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s12035-014-8662-4","article-title":"Role of cytosolic phospholipase A2 in oxidative and inflammatory signaling pathways in different cell types in the central nervous system","volume":"50","author":"Sun","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1111\/ceo.13126","article-title":"Imaging of the lamina cribrosa and its role in glaucoma: a review","volume":"46","author":"Tan","year":"2018","journal-title":"Clin. Exp. Ophthalmol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"995369","DOI":"10.3389\/fnana.2022.995369","article-title":"The heterogeneity of astrocytes in glaucoma","volume":"16","author":"Tang","year":"2022","journal-title":"Front. Neuroanat."},{"key":"B46","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1111\/micc.12108","article-title":"Novel contributions of the smoothelin-like 1 protein in vascular smooth muscle contraction and its potential involvement in myogenic tone","volume":"21","author":"Turner","year":"2014","journal-title":"Microcirculation"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.preteyeres.2015.06.003","article-title":"Glia\u2013neuron interactions in the mammalian retina","volume":"51","author":"Vecino","year":"2016","journal-title":"Prog. Retin. Eye Res."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2814","DOI":"10.3390\/ijms23052814","article-title":"Dysregulation of mTOR signaling after brain ischemia","volume":"23","author":"Villa-Gonz\u00e1lez","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.conb.2020.12.001","article-title":"Star power: the emerging role of astrocytes as neuronal partners during cortical plasticity","volume":"67","author":"Wahis","year":"2021","journal-title":"Curr. Opin. Neurobiol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/onc.2012.47","article-title":"Critical role of arachidonic acid-activated mTOR signaling in breast carcinogenesis and angiogenesis","volume":"32","author":"Wen","year":"2013","journal-title":"Oncogene"},{"key":"B51","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1007\/s00018-023-04801-z","article-title":"The role of blood flow in vessel remodeling and its regulatory mechanism during developmental angiogenesis","volume":"80","author":"Wen","year":"2023","journal-title":"Cell Mol. Life Sci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.amjms.2018.06.019","article-title":"Expression of cytosolic phospholipase A2 alpha in glioblastoma is associated with resistance to chemotherapy","volume":"356","author":"Yang","year":"2018","journal-title":"Am. J. Med. Sci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"2586","DOI":"10.1097\/CM9.0000000000001015","article-title":"Blood-retinal barrier as a converging pivot in understanding the initiation and development of retinal diseases","volume":"133","author":"Yang","year":"2020","journal-title":"Chin. Med. J. Engl."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.3390\/biom12121790","article-title":"Profiles of metabolic genes in Uncaria rhynchophylla and characterization of the critical enzyme involved in the biosynthesis of bioactive Compounds-(iso)Rhynchophylline","volume":"12","author":"Yang","year":"2022","journal-title":"Biomolecules"},{"key":"B55","doi-asserted-by":"publisher","first-page":"792764","DOI":"10.3389\/fncel.2021.792764","article-title":"Reactive astrocytes in central nervous system injury: subgroup and potential therapy","volume":"15","author":"Yu","year":"2021","journal-title":"Front. Cell Neurosci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"6391","DOI":"10.1523\/JNEUROSCI.6221-11.2012","article-title":"Genomic analysis of reactive astrogliosis","volume":"32","author":"Zamanian","year":"2012","journal-title":"J. Neurosci."},{"key":"B57","first-page":"4726","article-title":"Autophagy protects against cerebral ischemic reperfusion injury by inhibiting neuroinflammation","volume":"13","author":"Zha","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"B58","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s13578-020-00396-1","article-title":"mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges","volume":"10","author":"Zou","year":"2020","journal-title":"Cell Biosci."}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2025.1636882\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T04:16:03Z","timestamp":1755058563000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2025.1636882\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,13]]},"references-count":58,"alternative-id":["10.3389\/fmolb.2025.1636882"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2025.1636882","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,13]]},"article-number":"1636882"}}