{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:38:24Z","timestamp":1790786304779,"version":"4.1.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"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","award":["81300791"],"award-info":[{"award-number":["81300791"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin","doi-asserted-by":"crossref","award":["18JCYBJC26500"],"award-info":[{"award-number":["18JCYBJC26500"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Tianjin Science and Technology support key Project","award":["19YFZCSY00990"],"award-info":[{"award-number":["19YFZCSY00990"]}]},{"name":"Tianjin Health Research Project","award":["TJWJ2021MS042"],"award-info":[{"award-number":["TJWJ2021MS042"]}]},{"name":"Tianjin Health Research Project","award":["TJWJ2022XK037"],"award-info":[{"award-number":["TJWJ2022XK037"]}]},{"name":"Key project of Tianjin Eye Hospital","award":["YKZD2004"],"award-info":[{"award-number":["YKZD2004"]}]},{"name":"The 3rd Tianjin Talent Development Program and the High-level\u00a0Talents Program in TJHS"},{"name":"Tianjin key Medical Specialty Construction Project, Tianjin Key Medical Discipine (Specialty) Construction Project."},{"name":"Open Funding of the Ophthalmology Research Institute at Nankai University","award":["NKYKK202308"],"award-info":[{"award-number":["NKYKK202308"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biol Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Retinopathy of Prematurity (ROP) is a proliferative retinal vascular disease occurring in the retina of premature infants and is the main cause of childhood blindness. Nowadays anti-VEGF and retinal photocoagulation are mainstream treatments for ROP, but they develop a variety of complications. Hydrogen (H\n                      <jats:sub>2<\/jats:sub>\n                      ) is widely considered as a useful neuroprotective and antioxidative therapeutic method for hypoxic-ischemic disease without toxic effects. However, whether H\n                      <jats:sub>2<\/jats:sub>\n                      provides physiological angiogenesis promotion, neovascularization suppression and glial protection in the progression of ROP is largely unknown.This study aims to investigate the effects of H\n                      <jats:sub>2<\/jats:sub>\n                      on retinal angiogenesis, neovascularization and neuroglial dysfunction in the retinas of oxygen-induced retinopathy (OIR) mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, mice that were seven days old and either wild-type (WT) or Nrf2-deficient (\n                      <jats:italic>Nrf2\u2212\/\u2212<\/jats:italic>\n                      ) were exposed to 75% oxygen for 5 days and then returned to normal air conditions. Different stages of hydrogen gas (H\n                      <jats:sub>2<\/jats:sub>\n                      ) inhalation were administered. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. To count the number of neovascularization endothelial nuclei, routine HE staining of retinal sections was conducted. Immunohistochemistry was performed using DyLight 594 labeled GSL I-isolectin B4 (IB4), as well as primary antibodies against proliferating cell nuclear antigen (PCNA), glial fibrillary acidic protein (GFAP), and Iba-1. Western blots were used to measure the expression of NF-E2-related factor 2 (\n                      <jats:italic>Nrf2<\/jats:italic>\n                      ), vascular endothelial growth factor (\n                      <jats:italic>VEGF<\/jats:italic>\n                      ),\n                      <jats:italic>Notch1<\/jats:italic>\n                      ,\n                      <jats:italic>Dll4<\/jats:italic>\n                      , and\n                      <jats:italic>HIF-1\u03b1.<\/jats:italic>\n                      Additionally, the expression of target genes such as\n                      <jats:italic>NQO1, HO-1, Notch1, Hey1, Hey2<\/jats:italic>\n                      , and\n                      <jats:italic>Dll4<\/jats:italic>\n                      was measured. Human umbilical vein endothelial cells (HUVECs) treated with H\n                      <jats:sub>2<\/jats:sub>\n                      under hypoxia were used as an in vitro model. RT-PCR was used to evaluate the mRNA expression of\n                      <jats:italic>Nrf2, Notch\/Dll4<\/jats:italic>\n                      , and the target genes. The expression of reactive oxygen species (ROS) was observed using immunofluorescence staining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our results indicate that 3\u20134% H\n                      <jats:sub>2<\/jats:sub>\n                      does not disturb retinal physiological angiogenesis, but ameliorates vaso-obliteration and neovascularization in OIR mice. Moreover, H\n                      <jats:sub>2<\/jats:sub>\n                      prevents the decreased density and reverses the morphologic and functional changes in retinal astrocytes caused by oxygen-induced injury. In addition, H\n                      <jats:sub>2<\/jats:sub>\n                      inhalation reduces microglial activation, especially in the area of neovascularization in OIR mice. H\n                      <jats:sub>2<\/jats:sub>\n                      plays a protective role in vascular regeneration by promoting\n                      <jats:italic>Nrf2<\/jats:italic>\n                      activation and suppressing the\n                      <jats:italic>Dll4<\/jats:italic>\n                      -induced\n                      <jats:italic>Notch<\/jats:italic>\n                      signaling pathway in vivo. Also, H\n                      <jats:sub>2<\/jats:sub>\n                      promotes the proliferation of HUVECs under hypoxia by negatively regulating the\n                      <jats:italic>Dll4\/Notch<\/jats:italic>\n                      pathway and reducing ROS levels through\n                      <jats:italic>Nrf2<\/jats:italic>\n                      pathway aligning with our findings in vivo.Moreover, the retinal oxygen-sensing mechanisms (\n                      <jats:italic>HIF-1\u03b1\/VEGF)<\/jats:italic>\n                      are also involved in hydrogen-mediated retinal revascularization and neovascularization suppression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Collectively, our results indicate that H\n                      <jats:sub>2<\/jats:sub>\n                      could be a promising therapeutic agent for POR treatment and that its beneficial effect in human ROP might involve the activation of the\n                      <jats:italic>Nrf2-Notch<\/jats:italic>\n                      axis as well as\n                      <jats:italic>HIF-1\u03b1\/VEGF<\/jats:italic>\n                      pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s40659-024-00515-z","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T03:03:15Z","timestamp":1719198195000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Molecular hydrogen promotes retinal vascular regeneration and attenuates neovascularization and neuroglial dysfunction in oxygen-induced retinopathy mice"],"prefix":"10.1186","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7486-0044","authenticated-orcid":false,"given":"Yatu","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqiang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqi","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keliang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,24]]},"reference":[{"key":"515_CR1","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1016\/S0140-6736(13)60178-6","volume":"382","author":"A Hellstr\u00f6m","year":"2013","unstructured":"Hellstr\u00f6m A, Smith LE, Dammann O. Retinopathy of prematurity. Lancet. 2013;382:1445\u201357.","journal-title":"Lancet"},{"key":"515_CR2","unstructured":"Brown AC, Nwanyanwu K. Retinopathy of Prematurity. 2023."},{"key":"515_CR3","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.survophthal.2016.12.004","volume":"62","author":"ME Hartnett","year":"2017","unstructured":"Hartnett ME. Advances in understanding and management of retinopathy of prematurity. Surv Ophthalmol. 2017;62:257\u201376.","journal-title":"Surv Ophthalmol"},{"key":"515_CR4","first-page":"101","volume":"35","author":"LE Smith","year":"1994","unstructured":"Smith LE, Wesolowski E, McLellan A, Kostyk SK, D\u2019Amato R, Sullivan R, et al. Oxygen-induced retinopathy in the mouse. Invest Ophth Vis Sci. 1994;35:101\u201311.","journal-title":"Invest Ophth Vis Sci"},{"key":"515_CR5","doi-asserted-by":"publisher","first-page":"d1030","DOI":"10.2741\/1056","volume":"8","author":"A Madan","year":"2003","unstructured":"Madan A, Penn JS. Animal models of oxygen-induced retinopathy. Front Biosci. 2003;8:d1030\u201343.","journal-title":"Front Biosci"},{"key":"515_CR6","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1097\/ICU.0000000000000783","volume":"32","author":"JM Barnett","year":"2021","unstructured":"Barnett JM, Hubbard GB. Complications of retinopathy of prematurity treatment. Curr Opin Ophthalmol. 2021;32:475\u201381.","journal-title":"Curr Opin Ophthalmol"},{"key":"515_CR7","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1177\/1120672118770557","volume":"29","author":"J Liang","year":"2019","unstructured":"Liang J. Systematic review and meta-analysis of the negative outcomes of retinopathy of prematurity treated with laser photocoagulation. Eur J Ophthalmol. 2019;29:223\u20138.","journal-title":"Eur J Ophthalmol"},{"key":"515_CR8","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1111\/apa.13586","volume":"105","author":"JC Rivera","year":"2016","unstructured":"Rivera JC, Madaan A, Zhou TE, Chemtob S. Review of the mechanisms and therapeutic avenues for retinal and choroidal vascular dysfunctions in retinopathy of prematurity. Acta Paediatr. 2016;105:1421\u201333.","journal-title":"Acta Paediatr"},{"key":"515_CR9","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.ophtha.2014.07.050","volume":"122","author":"ME Hartnett","year":"2015","unstructured":"Hartnett ME. Pathophysiology and mechanisms of severe retinopathy of prematurity. Ophthalmology. 2015;122:200\u201310.","journal-title":"Ophthalmology"},{"key":"515_CR10","first-page":"D9734","volume":"1","author":"MJ Sankar","year":"2018","unstructured":"Sankar MJ, Sankar J, Chandra P. Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity. Cochrane Database Syst Rev. 2018;1:D9734.","journal-title":"Cochrane Database Syst Rev"},{"key":"515_CR11","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1001\/jamapediatrics.2017.4838","volume":"172","author":"A Stahl","year":"2018","unstructured":"Stahl A, Krohne TU, Eter N, Oberacher-Velten I, Guthoff R, Meltendorf S, et al. Comparing alternative ranibizumab dosages for safety and efficacy in retinopathy of prematurity: a randomized clinical trial. JAMA Pediatr. 2018;172:278\u201386.","journal-title":"JAMA Pediatr"},{"key":"515_CR12","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1016\/j.ophtha.2020.11.012","volume":"128","author":"CY Tsai","year":"2021","unstructured":"Tsai CY, Yeh PT, Tsao PN, Chung YE, Chang YS, Lai TT. Neurodevelopmental outcomes after bevacizumab treatment for retinopathy of prematurity: a meta-analysis. Ophthalmology. 2021;128:877\u201388.","journal-title":"Ophthalmology"},{"key":"515_CR13","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1038\/nm1577","volume":"13","author":"I Ohsawa","year":"2007","unstructured":"Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007;13:688\u201394.","journal-title":"Nat Med"},{"key":"515_CR14","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/2045-9912-3-10","volume":"3","author":"BJ Dixon","year":"2013","unstructured":"Dixon BJ, Tang J, Zhang JH. The evolution of molecular hydrogen: a noteworthy potential therapy with clinical significance. Med Gas Res. 2013;3:10.","journal-title":"Med Gas Res"},{"key":"515_CR15","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1152\/jappl.1994.76.3.1113","volume":"76","author":"JH Abraini","year":"1994","unstructured":"Abraini JH, Gardette-Chauffour MC, Martinez E, Rostain JC, Lemaire C. Psychophysiological reactions in humans during an open sea dive to 500 m with a hydrogen-helium-oxygen mixture. J Appl Physiol. 1994;76:1113\u20138.","journal-title":"J Appl Physiol"},{"key":"515_CR16","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41419-019-1525-1","volume":"10","author":"Y Han","year":"2019","unstructured":"Han Y, Shang Q, Yao J, Ji Y. Hydrogen sulfide: a gaseous signaling molecule modulates tissue homeostasis: implications in ophthalmic diseases. Cell Death Dis. 2019;10:293.","journal-title":"Cell Death Dis"},{"key":"515_CR17","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1146\/annurev.pharmtox.46.120604.141046","volume":"47","author":"TW Kensler","year":"2007","unstructured":"Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol. 2007;47:89\u2013116.","journal-title":"Annu Rev Pharmacol"},{"key":"515_CR18","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.mrrev.2007.11.006","volume":"659","author":"WO Osburn","year":"2008","unstructured":"Osburn WO, Kensler TW. Nrf2 signaling: an adaptive response pathway for protection against environmental toxic insults. Mutat Res-Fund Mol M. 2008;659:31\u20139.","journal-title":"Mutat Res-Fund Mol M"},{"key":"515_CR19","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1167\/iovs.62.6.25","volume":"62","author":"Z Huang","year":"2021","unstructured":"Huang Z, Ng TK, Chen W, Sun X, Huang D, Zheng D, et al. Nattokinase attenuates retinal neovascularization via modulation of Nrf2\/HO-1 and glial activation. Invest Ophth Vis Sci. 2021;62:25.","journal-title":"Invest Ophth Vis Sci"},{"key":"515_CR20","doi-asserted-by":"publisher","first-page":"E3910","DOI":"10.1073\/pnas.1309276110","volume":"110","author":"Y Wei","year":"2013","unstructured":"Wei Y, Gong J, Thimmulappa RK, Kosmider B, Biswal S, Duh EJ. Nrf2 acts cell-autonomously in endothelium to regulate tip cell formation and vascular branching. Proc Natl Acad Sci USA. 2013;110:E3910\u20138.","journal-title":"Proc Natl Acad Sci USA"},{"key":"515_CR21","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12473","volume":"64","author":"Y Xu","year":"2018","unstructured":"Xu Y, Lu X, Hu Y, Yang B, Tsui CK, Yu S, et al. Melatonin attenuated retinal neovascularization and neuroglial dysfunction by inhibition of HIF-1\u03b1-VEGF pathway in oxygen-induced retinopathy mice. J Pineal Res. 2018;64: e12473.","journal-title":"J Pineal Res"},{"key":"515_CR22","doi-asserted-by":"publisher","first-page":"E6927","DOI":"10.1073\/pnas.1512683112","volume":"112","author":"Y Wei","year":"2015","unstructured":"Wei Y, Gong J, Xu Z, Thimmulappa RK, Mitchell KL, Welsbie DS, et al. Nrf2 in ischemic neurons promotes retinal vascular regeneration through regulation of semaphorin 6A. Proc Natl Acad Sci USA. 2015;112:E6927\u201336.","journal-title":"Proc Natl Acad Sci USA"},{"key":"515_CR23","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1016\/S0891-5849(02)01005-5","volume":"33","author":"N Maulik","year":"2002","unstructured":"Maulik N, Das DK. Redox signaling in vascular angiogenesis. Free Radical Bio Med. 2002;33:1047\u201360.","journal-title":"Free Radical Bio Med"},{"key":"515_CR24","doi-asserted-by":"publisher","first-page":"2788","DOI":"10.3390\/ijms24032788","volume":"24","author":"Q Shi","year":"2023","unstructured":"Shi Q, Li S, Lyu Q, Zhang S, Bai Y, Ma J. Hypoxia inhibits cell cycle progression and cell proliferation in brain microvascular endothelial cells via the miR-212\u20133p\/MCM2 axis. Int J Mol Sci. 2023;24:2788.","journal-title":"Int J Mol Sci"},{"key":"515_CR25","doi-asserted-by":"publisher","first-page":"3789","DOI":"10.1007\/s00018-008-8305-x","volume":"65","author":"SN Naryzhny","year":"2008","unstructured":"Naryzhny SN. Proliferating cell nuclear antigen: a proteomics view. Cell Mol Life Sci. 2008;65:3789\u2013808.","journal-title":"Cell Mol Life Sci"},{"key":"515_CR26","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.exer.2009.12.012","volume":"90","author":"K Uno","year":"2010","unstructured":"Uno K, Prow TW, Bhutto IA, Yerrapureddy A, McLeod DS, Yamamoto M, et al. Role of Nrf2 in retinal vascular development and the vaso-obliterative phase of oxygen-induced retinopathy. Exp Eye Res. 2010;90:493\u2013500.","journal-title":"Exp Eye Res"},{"key":"515_CR27","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s12974-022-02400-6","volume":"19","author":"R Dang","year":"2022","unstructured":"Dang R, Wang M, Li X, Wang H, Liu L, Wu Q, et al. Edaravone ameliorates depressive and anxiety-like behaviors via Sirt1\/Nrf2\/HO-1\/Gpx4 pathway. J Neuroinflamm. 2022;19:41.","journal-title":"J Neuroinflamm"},{"key":"515_CR28","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1038\/s41390-022-02211-8","volume":"93","author":"S Su","year":"2023","unstructured":"Su S, Zou P, Yang G, Wang Y, Liu L, Liu Y, et al. Propranolol ameliorates retinopathy of prematurity in mice by downregulating HIF-1\u03b1 via the PI3K\/Akt\/ERK pathway. Pediatr Res. 2023;93:1250\u20137.","journal-title":"Pediatr Res"},{"key":"515_CR29","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.preteyeres.2017.09.002","volume":"62","author":"T Chan-Ling","year":"2018","unstructured":"Chan-Ling T, Gole GA, Quinn GE, Adamson SJ, Darlow BA. Pathophysiology, screening and treatment of ROP: a multi-disciplinary perspective. Prog Retin Eye Res. 2018;62:77\u2013119.","journal-title":"Prog Retin Eye Res"},{"key":"515_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pharmthera.2014.04.006","volume":"144","author":"S Ohta","year":"2014","unstructured":"Ohta S. Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine. Pharmacol Therapeut. 2014;144:1\u201311.","journal-title":"Pharmacol Therapeut"},{"key":"515_CR31","unstructured":"Yaws CL. Matheson gas data book. (No Title). 2001."},{"key":"515_CR32","doi-asserted-by":"publisher","first-page":"592","DOI":"10.2174\/1381612826666201019103446","volume":"27","author":"H Takahashi","year":"2021","unstructured":"Takahashi H. Application of hydrogen in ophthalmology. Curr Pharm Design. 2021;27:592\u20134.","journal-title":"Curr Pharm Design"},{"key":"515_CR33","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.lfs.2016.04.015","volume":"153","author":"Q Zhang","year":"2016","unstructured":"Zhang Q, Tao Y, Zhang ZM. Hydrogen-rich Saline is ineffective in oxygen-induced retinopathy. Life Sci. 2016;153:17\u201322.","journal-title":"Life Sci"},{"key":"515_CR34","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.biocel.2009.10.006","volume":"42","author":"P Sapieha","year":"2010","unstructured":"Sapieha P, Hamel D, Shao Z, Rivera JC, Zaniolo K, Joyal JS, et al. Proliferative retinopathies: angiogenesis that blinds. Int J Biochem Cell B. 2010;42:5\u201312.","journal-title":"Int J Biochem Cell B"},{"key":"515_CR35","doi-asserted-by":"publisher","first-page":"L535","DOI":"10.1152\/ajplung.00002.2010","volume":"299","author":"J Nijmeh","year":"2010","unstructured":"Nijmeh J, Moldobaeva A, Wagner EM. Role of ROS in ischemia-induced lung angiogenesis. Am J Physiol-Lung C. 2010;299:L535\u201341.","journal-title":"Am J Physiol-Lung C"},{"key":"515_CR36","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1161\/ATVBAHA.110.204123","volume":"30","author":"S Ichihara","year":"2010","unstructured":"Ichihara S, Yamada Y, Liu F, Murohara T, Itoh K, Yamamoto M, et al. Ablation of the transcription factor Nrf2 promotes ischemia-induced neovascularization by enhancing the inflammatory response. Arterioscl Throm Vas. 2010;30:1553\u201361.","journal-title":"Arterioscl Throm Vas"},{"key":"515_CR37","doi-asserted-by":"publisher","first-page":"3221","DOI":"10.1007\/s00018-016-2223-0","volume":"73","author":"A Loboda","year":"2016","unstructured":"Loboda A, Damulewicz M, Pyza E, Jozkowicz A, Dulak J. Role of Nrf2\/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism. Cell Mol Life Sci. 2016;73:3221\u201347.","journal-title":"Cell Mol Life Sci"},{"key":"515_CR38","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1002\/glia.20997","volume":"58","author":"A Weidemann","year":"2010","unstructured":"Weidemann A, Krohne TU, Aguilar E, Kurihara T, Takeda N, Dorrell MI, et al. Astrocyte hypoxic response is essential for pathological but not developmental angiogenesis of the retina. Glia. 2010;58:1177\u201385.","journal-title":"Glia"},{"key":"515_CR39","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1016\/j.omtn.2019.04.029","volume":"16","author":"W Xu","year":"2019","unstructured":"Xu W, Wu Y, Hu Z, Sun L, Dou G, Zhang Z, et al. Exosomes from microglia attenuate photoreceptor injury and neovascularization in an animal model of retinopathy of prematurity. Mol Ther-Nucl Acids. 2019;16:778\u201390.","journal-title":"Mol Ther-Nucl Acids"},{"key":"515_CR40","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1002\/glia.23810","volume":"68","author":"M Boeck","year":"2020","unstructured":"Boeck M, Thien A, Wolf J, Hagemeyer N, Laich Y, Yusuf D, et al. Temporospatial distribution and transcriptional profile of retinal microglia in the oxygen-induced retinopathy mouse model. Glia. 2020;68:1859\u201373.","journal-title":"Glia"},{"key":"515_CR41","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.preteyeres.2014.11.004","volume":"45","author":"M Karlstetter","year":"2015","unstructured":"Karlstetter M, Scholz R, Rutar M, Wong WT, Provis JM, Langmann T. Retinal microglia: just bystander or target for therapy? Prog Retin Eye Res. 2015;45:30\u201357.","journal-title":"Prog Retin Eye Res"},{"key":"515_CR42","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1002\/glia.20900","volume":"58","author":"MI Dorrell","year":"2010","unstructured":"Dorrell MI, Aguilar E, Jacobson R, Trauger SA, Friedlander J, Siuzdak G, et al. Maintaining retinal astrocytes normalizes revascularization and prevents vascular pathology associated with oxygen-induced retinopathy. Glia. 2010;58:43\u201354.","journal-title":"Glia"},{"key":"515_CR43","doi-asserted-by":"publisher","first-page":"5102","DOI":"10.1182\/blood-2009-07-230284","volume":"115","author":"GA Strasser","year":"2010","unstructured":"Strasser GA, Kaminker JS, Tessier-Lavigne M. Microarray analysis of retinal endothelial tip cells identifies CXCR4 as a mediator of tip cell morphology and branching. Blood. 2010;115:5102\u201310.","journal-title":"Blood"},{"key":"515_CR44","doi-asserted-by":"publisher","first-page":"5758","DOI":"10.1038\/ncomms6758","volume":"5","author":"C Xu","year":"2014","unstructured":"Xu C, Hasan SS, Schmidt I, Rocha SF, Pitulescu ME, Bussmann J, et al. Arteries are formed by vein-derived endothelial tip cells. Nat Commun. 2014;5:5758.","journal-title":"Nat Commun"},{"key":"515_CR45","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.preteyeres.2012.04.004","volume":"31","author":"J Kur","year":"2012","unstructured":"Kur J, Newman EA, Chan-Ling T. Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease. Prog Retin Eye Res. 2012;31:377\u2013406.","journal-title":"Prog Retin Eye Res"},{"key":"515_CR46","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1161\/ATVBAHA.113.301331","volume":"33","author":"JC Rivera","year":"2013","unstructured":"Rivera JC, Sitaras N, Noueihed B, Hamel D, Madaan A, Zhou T, et al. Microglia and interleukin-1\u03b2 in ischemic retinopathy elicit microvascular degeneration through neuronal semaphorin-3A. Arterioscl Throm Vas. 2013;33:1881\u201391.","journal-title":"Arterioscl Throm Vas"},{"key":"515_CR47","first-page":"467","volume":"12","author":"MH Davies","year":"2006","unstructured":"Davies MH, Eubanks JP, Powers MR. Microglia and macrophages are increased in response to ischemia-induced retinopathy in the mouse retina. Mol Vis. 2006;12:467\u201377.","journal-title":"Mol Vis"},{"key":"515_CR48","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1002\/iub.1358","volume":"67","author":"A Szade","year":"2015","unstructured":"Szade A, Grochot-Przeczek A, Florczyk U, Jozkowicz A, Dulak J. Cellular and molecular mechanisms of inflammation-induced angiogenesis. IUBMB Life. 2015;67:145\u201359.","journal-title":"IUBMB Life"}],"container-title":["Biological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40659-024-00515-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40659-024-00515-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40659-024-00515-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T03:03:46Z","timestamp":1719198226000},"score":1,"resource":{"primary":{"URL":"https:\/\/biolres.biomedcentral.com\/articles\/10.1186\/s40659-024-00515-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,24]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["515"],"URL":"https:\/\/doi.org\/10.1186\/s40659-024-00515-z","relation":{},"ISSN":["0717-6287"],"issn-type":[{"value":"0717-6287","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,24]]},"assertion":[{"value":"17 January 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethics approval and consent to participate All animal studies were conducted in accordance with the Nankai University guidelines for the care and use of laboratory animals and were approved approved by the Institutional Animal Care and Use Committee at Nankai University(Approval No.NKYY-DWLL-2021-070)","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"43"}}