{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T09:41:06Z","timestamp":1764841266978,"version":"3.41.2"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T00:00:00Z","timestamp":1658793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>This study was conducted in order to test the expression of vasoactive substances within rat lamina cribrosa (LC) and optic nerve head (ONH) astrocytes, so as to investigate the role and potential mechanism of ONH astrocytes in vascular associated effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>LC tissue sections and primary cultured ONH astrocytes were obtained from adult Sprague-Dawley (SD) rats. Immunofluorescent staining was then used to detect the expression of vasoactive substances. Hyperoxia exposure was carried out both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>, after which nitric oxide (NO) levels in LC tissue and cell supernatant were detected. The variations of protein and gene expression associated with vasoactive substances were subsequently tested. ONH astrocytes and vascular smooth muscle cells (VSMCs) were then incubated in a direct co-culture manner. Morphological parameters of VSMCs were finally analyzed in order to evaluate cell contraction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Endothelin-1 (ET-1), nitric oxide synthase (NOS) and renin-angiotensin system (RAS) were detected in both LC tissue and ONH astrocytes. Retinal vessel diameter was found obviously decreased following hyperoxia exposure. Moreover, hyperoxia inhibited NO production both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. ET-1 and RAS elements were observed to be upregulated, whereas NOS was downregulated. In ONH astrocytes and VSMCs co-culture system, the length-to-width ratio of VSMCs was shown to significantly increase on days 3 and 7 in hyperoxia compared with normoxia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>There is an abundance of expression of vasoactive substances within LC tissue and ONH astrocytes. The contractile response of VSMCs in the co-culture system provided direct evidence for the involvement of ONH astrocytes in vascular associated effects, which may signify a potentially novel direction for future research.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2022.943986","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T16:54:16Z","timestamp":1658854456000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Optic nerve head astrocytes contribute to vascular associated effects"],"prefix":"10.3389","volume":"9","author":[{"given":"Yanmin","family":"Dong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobing","family":"Qian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leilei","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongguang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujie","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanwen","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianying","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.exer.2016.05.006","article-title":"Identification and localization of lamina cribrosa cells in the human optic nerve head","volume":"147","author":"Tovar-Vidales","year":"2016","journal-title":"Exp Eye Res."},{"key":"B2","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":"B3","first-page":"758","article-title":"Expression of ciliary neurotrophic factor (CNTF) and its tripartite receptor complex by cells of the human optic nerve head","volume":"13","author":"Liu","year":"2007","journal-title":"Mol Vis."},{"key":"B4","first-page":"2315","article-title":"Neurotrophin and neurotrophin receptor expression by cells of the human lamina cribrosa","volume":"42","author":"Lambert","year":"2001","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/1471-2202-5-51","article-title":"Neurotrophin and Trk expression by cells of the human lamina cribrosa following oxygen-glucose deprivation","volume":"5","author":"Lambert","year":"2004","journal-title":"BMC Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1167\/iovs.16-20804","article-title":"Glial cell contribution to basal vessel diameter and Pressure-Initiated vascular responses in rat retina","volume":"58","author":"Li","year":"2017","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"3726","DOI":"10.1167\/iovs.11-9316","article-title":"Involvement of glial cells in the autoregulation of optic nerve head blood flow in rabbits","volume":"53","author":"Shibata","year":"2012","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature09613","article-title":"Glial and neuronal control of brain blood flow","volume":"468","author":"Attwell","year":"2010","journal-title":"Nature."},{"key":"B9","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s41467-019-13956-y","article-title":"Astrocytes monitor cerebral perfusion and control systemic circulation to maintain brain blood flow","volume":"11","author":"Marina","year":"2020","journal-title":"Nat Commun."},{"key":"B10","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":"B11","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1002\/glia.23189","article-title":"Astrocytes follow ganglion cell axons to establish an angiogenic template during retinal development","volume":"65","author":"O'Sullivan","year":"2017","journal-title":"Glia."},{"key":"B12","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1002\/1096-9861(20000108)429:2<253::AID-CNE6>3.0.CO;2-S","article-title":"Confocal microscopic study of glial-vascular relationships in the retinas of pigmented rats","volume":"429","author":"Zahs","year":"2001","journal-title":"J Comp Neurol"},{"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":"Garcia-Bermudez","year":"2021","journal-title":"Front Neurol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.jphs.2020.12.009","article-title":"Potential roles of astrocytes and muller cells in the pathogenesis of glaucoma","volume":"145","author":"Shinozaki","year":"2021","journal-title":"J Pharmacol Sci."},{"key":"B15","first-page":"78","article-title":"Cell culture of the human lamina cribrosa","volume":"29","author":"Hernandez","year":"1988","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.exer.2015.05.023","article-title":"Plate reader-based cell viability assays for glioprotection using primary rat optic nerve head astrocytes","volume":"138","author":"Kaja","year":"2015","journal-title":"Exp Eye Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1161\/01.HYP.0000119191.33112.9c","article-title":"Isolation and culture of arterial smooth muscle cells from human placenta","volume":"43","author":"Leik","year":"2004","journal-title":"Hypertension."},{"key":"B18","first-page":"320","article-title":"Morphometric assessment of the central retinal artery and vein in the optic nerve head","volume":"28","author":"Taylor","year":"1993","journal-title":"Can J Ophthalmol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1167\/iovs.10-6366","article-title":"Morphometric characteristics of central retinal artery and vein endothelium in the normal human optic nerve head","volume":"52","author":"Kang","year":"2011","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"354645","DOI":"10.1155\/2010\/354645","article-title":"Endothelin-1 role in human eye: a review","volume":"2010","author":"Salvatore","year":"2010","journal-title":"J Ophthalmol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.exer.2014.06.018","article-title":"Role of nitric oxide synthase isoforms for ophthalmic artery reactivity in mice","volume":"127","author":"Laspas","year":"2014","journal-title":"Exp Eye Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1080\/07853890.2020.1758341","article-title":"Local ocular renin-angiotensin-aldosterone system: Any connection with intraocular pressure? A comprehensive review","volume":"52","author":"Holappa","year":"2020","journal-title":"Ann Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"122","DOI":"10.2174\/1874364101711010122","article-title":"Many faces of renin-angiotensin system - focus on eye","volume":"11","author":"Holappa","year":"2017","journal-title":"Open Ophthalmol J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.exer.2014.02.008","article-title":"Comparative quantitative study of astrocytes and capillary distribution in optic nerve laminar regions","volume":"121","author":"Balaratnasingam","year":"2014","journal-title":"Exp Eye Res."},{"key":"B25","first-page":"1702","article-title":"Microvasculature of the rat optic nerve head","volume":"40","author":"Morrison","year":"1999","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/0039-6257(94)90157-0","article-title":"The vascular endothelium as a regulator of the ocular circulation: a new concept in ophthalmology?","volume":"39","author":"Haefliger","year":"1994","journal-title":"Surv Ophthalmol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/S1350-9462(00)0002-3","article-title":"Endothelium-dependent vasoactive modulation in the ophthalmic circulation","volume":"20","author":"Haefliger","year":"2001","journal-title":"Prog Retin Eye Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/S1350-9462(01)00005-2","article-title":"Blood flow in the optic nerve head and factors that may influence it","volume":"20","author":"Hayreh","year":"2001","journal-title":"Prog Retin Eye Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/S1350-9462(01)00014-3","article-title":"Role of nitric oxide in the control of ocular blood flow","volume":"20","author":"Schmetterer","year":"2001","journal-title":"Prog Retin Eye Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.1167\/iovs.12-11406","article-title":"Role of nitric oxide in optic nerve head blood flow regulation during isometric exercise in healthy humans","volume":"54","author":"Schmidl","year":"2013","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"965","DOI":"10.3109\/02713683.2013.794247","article-title":"Relaxation of porcine retinal arterioles during acute hypoxia in vitro depends on prostaglandin and NO synthesis in the perivascular retina","volume":"38","author":"Kringelholt","year":"2013","journal-title":"Curr Eye Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"4595","DOI":"10.1167\/iovs.07-1667","article-title":"Role of nitric oxide in regulation of retinal blood flow in response to hyperoxia in cats","volume":"49","author":"Izumi","year":"2008","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"3113","DOI":"10.1167\/iovs.14-15854","article-title":"Role of neuronal nitric oxide synthase in regulating retinal blood flow during flicker-induced hyperemia in cats","volume":"56","author":"Yoshioka","year":"2015","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.niox.2018.04.010","article-title":"The nitric oxide-guanylate cyclase pathway and glaucoma","volume":"77","author":"Wareham","year":"2018","journal-title":"Nitric Oxide."},{"key":"B35","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1177\/1470320314549791","article-title":"Expression of classical components of the renin-angiotensin system in the human eye","volume":"16","author":"White","year":"2015","journal-title":"J Renin Angiotensin Aldosterone Syst."},{"key":"B36","first-page":"1443","article-title":"Expression and cellular localization of the Mas receptor in the adult and developing mouse retina","volume":"20","author":"Prasad","year":"2014","journal-title":"Mol Vis."},{"key":"B37","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1080\/02713683.2022.2029907","article-title":"Compromised blood flow in the optic nerve head after systemic administration of aldosterone in rats: a possible rat model of retinal ganglion cell loss","volume":"47","author":"Wada","year":"2022","journal-title":"Curr Eye Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"610","DOI":"10.3390\/antiox11040610","article-title":"The retinal renin-angiotensin-aldosterone system: implications for glaucoma","volume":"11","author":"Hirooka","year":"2022","journal-title":"Antioxidants."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.943986\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T16:54:30Z","timestamp":1658854470000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.943986\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,26]]},"references-count":38,"alternative-id":["10.3389\/fmed.2022.943986"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.943986","relation":{},"ISSN":["2296-858X"],"issn-type":[{"type":"electronic","value":"2296-858X"}],"subject":[],"published":{"date-parts":[[2022,7,26]]},"article-number":"943986"}}