{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T23:13:00Z","timestamp":1793747580090,"version":"4.6.1"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004775","name":"Natural Science Foundation of Gansu Province","doi-asserted-by":"publisher","award":["21JR7RA837"],"award-info":[{"award-number":["21JR7RA837"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Experimental Eye Research"],"published-print":{"date-parts":[[2023,8]]},"DOI":"10.1016\/j.exer.2023.109539","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T12:23:26Z","timestamp":1686572606000},"page":"109539","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":33,"special_numbering":"C","title":["Rapamycin inhibits corneal inflammatory response and neovascularization in a mouse model of corneal alkali burn"],"prefix":"10.1016","volume":"233","author":[{"given":"Jiande","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangyuan","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongpeng","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minrui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.exer.2023.109539_bib1","doi-asserted-by":"crossref","first-page":"627","DOI":"10.14202\/vetworld.2018.627-635","article-title":"The crucial roles of inflammatory mediators in inflammation: a review","volume":"11","author":"Abdulkhaleq","year":"2018","journal-title":"Vet. World"},{"key":"10.1016\/j.exer.2023.109539_bib2","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jtos.2016.09.002","article-title":"Current and upcoming therapies for ocular surface chemical injuries","volume":"15","author":"Baradaran-Rafii","year":"2017","journal-title":"Ocul. Surf."},{"key":"10.1016\/j.exer.2023.109539_bib3","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.jtos.2015.11.006","article-title":"Differential effects of dexamethasone and doxycycline on inflammation and MMP production in murine alkali-burned corneas associated with dry eye","volume":"14","author":"Bian","year":"2016","journal-title":"Ocul. Surf."},{"key":"10.1016\/j.exer.2023.109539_bib4","doi-asserted-by":"crossref","DOI":"10.3390\/ijms18030562","article-title":"Inhibition of NLRP3 inflammasome pathway by butyrate improves corneal wound healing in corneal alkali burn","author":"Bian","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.exer.2023.109539_bib5","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.survophthal.2015.11.006","article-title":"Matrix metalloproteinase 14 modulates signal transduction and angiogenesis in the cornea","volume":"61","author":"Chang","year":"2016","journal-title":"Surv. Ophthalmol."},{"key":"10.1016\/j.exer.2023.109539_bib6","doi-asserted-by":"crossref","DOI":"10.1155\/2013\/928315","article-title":"Matrix metalloproteinases: inflammatory regulators of cell behaviors in vascular formation and remodeling","volume":"2013","author":"Chen","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"10.1016\/j.exer.2023.109539_bib7","article-title":"Amniotic membrane transplantation for acute ocular burns","author":"Clare","year":"2022","journal-title":"Cochrane Database Syst. Rev."},{"key":"10.1016\/j.exer.2023.109539_bib8","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.biocel.2004.08.012","article-title":"Hypoxia-inducible factor 1: regulation by hypoxic and non-hypoxic activators","volume":"37","author":"D\u00e9ry","year":"2005","journal-title":"Int. J. Biochem. Cell Biol."},{"issue":"2","key":"10.1016\/j.exer.2023.109539_bib9","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/sj\/eye\/6700095","article-title":"Comparison of serum NO, TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels with grades of retinopathy in patients with diabetes mellitus","volume":"16","author":"Doganay","year":"2002","journal-title":"Eye"},{"key":"10.1016\/j.exer.2023.109539_bib10","doi-asserted-by":"crossref","first-page":"6108","DOI":"10.1167\/iovs.14-14736","article-title":"The role of toll-like receptor 4 in corneal epithelial wound healing","volume":"55","author":"Eslani","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2023.109539_bib11","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.ajo.2007.07.022","article-title":"Anti-angiogenic effects of ribonucleic acid interference targeting vascular endothelial growth factor and hypoxia-inducible factor-1\u03b1","volume":"144","author":"Forooghian","year":"2007","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.exer.2023.109539_bib12","first-page":"3046","article-title":"Rapamycin prevents endothelial cell migration by inhibiting the endothelial-to-mesenchymal transition and matrix metalloproteinase-2 and -9: an in vitro study","volume":"17","author":"Gao","year":"2011","journal-title":"Mol. Vis."},{"key":"10.1016\/j.exer.2023.109539_bib13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1080\/09273948.2016.1277247","article-title":"Roles of IL-6 in ocular inflammation: a review","volume":"26","author":"Ghasemi","year":"2018","journal-title":"Ocul. Immunol. Inflamm."},{"key":"10.1016\/j.exer.2023.109539_bib14","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.exer.2017.08.008","article-title":"TNF-\u03b1 upregulates HIF-1\u03b1 expression in pterygium fibroblasts and enhances their susceptibility to VEGF independent of hypoxia","volume":"164","author":"Kim","year":"2017","journal-title":"Exp. Eye Res."},{"issue":"25","key":"10.1016\/j.exer.2023.109539_bib15","doi-asserted-by":"crossref","DOI":"10.18632\/oncotarget.17256","article-title":"Rapamycin regulates macrophage activation by inhibiting NLRP3 inflammasome-p38 MAPK-NF\u03baB pathways in autophagy- and p62-dependent manners","volume":"8","author":"Ko","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.exer.2023.109539_bib16","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.micinf.2005.07.006","article-title":"Toll-like receptor 2-mediated expression of \u03b2-defensin-2 in human corneal epithelial cells","volume":"8","author":"Kumar","year":"2006","journal-title":"Microb. Infect."},{"key":"10.1016\/j.exer.2023.109539_bib17","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1167\/iovs.04-0753","article-title":"Inhibitory effect of rapamycin on corneal neovascularization in vitro and in vivo","volume":"46","author":"Kwon","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2023.109539_bib18","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1189\/jlb.0801757","article-title":"Enhancement by neutrophils of collagen degradation by corneal fibroblasts","volume":"74","author":"Li","year":"2003","journal-title":"J. Leukoc. Biol."},{"key":"10.1016\/j.exer.2023.109539_bib19","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2020.598056","article-title":"Laquinimod inhibits inflammation-induced angiogenesis in the cornea","volume":"7","author":"Li","year":"2020","journal-title":"Front. Med."},{"key":"10.1016\/j.exer.2023.109539_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.exer.2020.108399","article-title":"Rapamycin ameliorates corneal injury after alkali burn through methylation modification in mouse TSC1 and mTOR genes","volume":"203","author":"Li","year":"2021","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2023.109539_bib21","doi-asserted-by":"crossref","DOI":"10.1155\/2021\/2406646","article-title":"Topical vitamin C promotes the recovery of corneal alkali burns in mice","volume":"2021","author":"Li","year":"2021","journal-title":"J. Ophthalmol."},{"issue":"1","key":"10.1016\/j.exer.2023.109539_bib22","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0016712","article-title":"Anti-angiogenic and anti-inflammatory effects of SERPINA3K on corneal injury","volume":"6","author":"Liu","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.exer.2023.109539_bib23","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1038\/mi.2016.139","article-title":"CCR2\u2212 and CCR2+ corneal macrophages exhibit distinct characteristics and balance inflammatory responses after epithelial abrasion","volume":"10","author":"Liu","year":"2017","journal-title":"Mucosal Immunol."},{"key":"10.1016\/j.exer.2023.109539_bib24","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using realtime quantitative PCR and the 2 (-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.exer.2023.109539_bib25","doi-asserted-by":"crossref","DOI":"10.1097\/01.ico.0000248385.16896.34","article-title":"Alkali-induced corneal neovascularization is independent of CXCR2-mediated neutrophil infiltration","volume":"26","author":"Lu","year":"2007","journal-title":"Cornea"},{"issue":"2","key":"10.1016\/j.exer.2023.109539_bib27","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1634\/stemcells.2005-0046","article-title":"Reconstruction of chemically burned rat corneal surface by bone marrow-derived human mesenchymal stem cells","volume":"24","author":"Ma","year":"2006","journal-title":"Stem Cell."},{"key":"10.1016\/j.exer.2023.109539_bib28","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1001\/archopht.116.11.1470","article-title":"Inflammatory response in the early stages of wound healing after excimer laser keratectomy","volume":"116","author":"O'Brien","year":"1998","journal-title":"Arch. Ophthalmol."},{"key":"10.1016\/j.exer.2023.109539_bib29","doi-asserted-by":"crossref","DOI":"10.1016\/j.clim.2020.108464","article-title":"Targeting T-cell senescence and cytokine storm with rapamycin to prevent severe progression in COVID-19","volume":"216","author":"Omarjee","year":"2020","journal-title":"Clin. Immunol."},{"key":"10.1016\/j.exer.2023.109539_bib31","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1002\/stem.3036","article-title":"Inhibition of mTOR by rapamycin aggravates corneal epithelial stem cell deficiency by upregulating inflammatory response","volume":"37","author":"Park","year":"2019","journal-title":"Stem Cell."},{"key":"10.1016\/j.exer.2023.109539_bib30","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/s41422-020-0291-z","article-title":"Targeting immunometabolism as an anti-inflammatory strategy","volume":"30(4)","author":"P\u00e5lsson-McDermott","year":"2020","journal-title":"Cell Res"},{"key":"10.1016\/j.exer.2023.109539_bib32","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.21873\/invivo.12405","article-title":"Bioluminescence imaging of matrix metalloproteinases-2 and -9 activities in ethanol-injured cornea of mice","volume":"35","author":"Park","year":"2021","journal-title":"Vivo"},{"key":"10.1016\/j.exer.2023.109539_bib33","first-page":"2514","article-title":"Expression of vascular endothelial growth factor and its receptors in inflamed and vascularized human corneas","volume":"41","author":"Philipp","year":"2000","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2023.109539_bib34","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.exer.2004.08.023","article-title":"Delayed inflammation-associated corneal neovascularization in MMP-2-deficient mice","volume":"80","author":"Samolov","year":"2005","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2023.109539_bib35","first-page":"506","article-title":"Euthanasia method for mice in rapid time-course pulmonary pharmacokinetic studies","volume":"48","author":"Schoell","year":"2009","journal-title":"J Am Assoc Lab Anim Sci"},{"issue":"1","key":"10.1016\/j.exer.2023.109539_bib36","doi-asserted-by":"crossref","first-page":"15","DOI":"10.22336\/rjo.2019.4","article-title":"Corneal neovascularization: updates on pathophysiology, investigations & management","volume":"63","author":"Sharif","year":"2019","journal-title":"Romanian Journal of Ophthalmol"},{"key":"10.1016\/j.exer.2023.109539_bib37","doi-asserted-by":"crossref","first-page":"9596","DOI":"10.1038\/s41598-019-46116-9","article-title":"Pro-inflammatory role of NLRP3 inflammasome in experimental sterile corneal inflammation","volume":"9","author":"Shimizu","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.exer.2023.109539_bib38","doi-asserted-by":"crossref","first-page":"4452","DOI":"10.1167\/iovs.13-11684","article-title":"Chemical injury-induced corneal opacity and neovascularization reduced by rapamycin via TGF-\u03b21\/ERK pathways regulation","volume":"54","author":"Shin","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2023.109539_bib39","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.trsl.2021.05.005","article-title":"Immune responses to injury and their links to eye disease","volume":"236","author":"Stepp","year":"2021","journal-title":"Transl. Res."},{"key":"10.1016\/j.exer.2023.109539_bib40","article-title":"Ginkgo biloba leaf extract attenuates atherosclerosis in streptozotocin-induced diabetic ApoE-\/- mice by inhibiting endoplasmic reticulum stress via restoration of autophagy through the mTOR signaling pathway","volume":"2019","author":"Tian","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"10.1016\/j.exer.2023.109539_bib41","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1189\/jlb.0902436","article-title":"The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization","volume":"74","author":"Tsutsumi","year":"2003","journal-title":"J. Leukoc. Biol."},{"issue":"15","key":"10.1016\/j.exer.2023.109539_bib42","doi-asserted-by":"crossref","first-page":"4316","DOI":"10.7150\/ijbs.62868","article-title":"Berberine improves insulin-induced diabetic retinopathy through exclusively suppressing Akt\/mTOR-mediated HIF-1\u03b1\/VEGF activation in retina endothelial cells","volume":"17","author":"Wang","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"10.1016\/j.exer.2023.109539_bib43","doi-asserted-by":"crossref","first-page":"50","DOI":"10.6002\/ect.2020.0111","article-title":"Influence of an early application of mammalian target of rapamycin inhibitors everolimus and sirolimus on acute vascular inflammatory responses after ischemia-reperfusion injury","volume":"19","author":"Wenzel","year":"2021","journal-title":"Exp. Clin. Transplant."},{"key":"10.1016\/j.exer.2023.109539_bib44","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S1350-9462(98)00017-2","article-title":"Stromal-epithelial interactions in the cornea","volume":"18","author":"Wilson","year":"1999","journal-title":"Prog. Retin. Eye Res."},{"key":"10.1016\/j.exer.2023.109539_bib45","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.biopha.2018.10.091","article-title":"Tetramethylpyrazine (TMP) ameliorates corneal neovascularization via regulating cell infiltration into cornea after alkali burn","volume":"109","author":"Wu","year":"2019","journal-title":"Biomed. Pharmacother."},{"issue":"5","key":"10.1016\/j.exer.2023.109539_bib46","first-page":"712","article-title":"Production of interleukin-1\u03b2 related to mammalian target of rapamycin\/Toll-like receptor 4 signaling pathway during Aspergillus fumigatus infection of the mouse cornea","volume":"11","author":"Xu","year":"2018","journal-title":"Int. J. Ophthalmol."},{"issue":"2","key":"10.1016\/j.exer.2023.109539_bib48","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0030842","article-title":"Role of mesenchymal stem cells on cornea wound healing induced by acute alkali burn","volume":"7","author":"Yao","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.exer.2023.109539_bib49","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2020.106902","article-title":"Neutrophil extracellular traps promote corneal neovascularization-induced by alkali burn","volume":"88","author":"Yuan","year":"2020","journal-title":"Int. Immunopharm."},{"key":"10.1016\/j.exer.2023.109539_bib50","doi-asserted-by":"crossref","first-page":"189","DOI":"10.2174\/187152506777698344","article-title":"Cytokines and hormones in the regulation of hypoxia inducible factor-1\u03b1 (HIF-1\u03b1)","volume":"4","author":"Zhou","year":"2006","journal-title":"Cardiovasc. Hematol. Agents Med. Chem."},{"key":"10.1016\/j.exer.2023.109539_bib51","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1080\/13813455.2019.1609996","article-title":"Role of mammalian target of rapamycin in regulating HIF-1\u03b1 and vascular endothelial growth factor signals in glaucoma","volume":"127","author":"Zhou","year":"2021","journal-title":"Arch. Physiol. Biochem."}],"container-title":["Experimental Eye Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483523001604?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483523001604?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T05:36:15Z","timestamp":1762148175000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014483523001604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":49,"alternative-id":["S0014483523001604"],"URL":"https:\/\/doi.org\/10.1016\/j.exer.2023.109539","relation":{},"ISSN":["0014-4835"],"issn-type":[{"value":"0014-4835","type":"print"}],"subject":[],"published":{"date-parts":[[2023,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Rapamycin inhibits corneal inflammatory response and neovascularization in a mouse model of corneal alkali burn","name":"articletitle","label":"Article Title"},{"value":"Experimental Eye Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.exer.2023.109539","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"109539"}}