{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:16:52Z","timestamp":1788779812290,"version":"build-2803163510"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.fr","clinicalkey.jp","clinicalkey.com.au","clinicalkey.es","clinicalkey.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Tissue and Cell"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1016\/j.tice.2025.102817","type":"journal-article","created":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T16:27:46Z","timestamp":1740846466000},"page":"102817","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Nintedanib abrogates patient vitreous-induced Akt activation and tube formation of human retinal microvascular endothelial cells"],"prefix":"10.1016","volume":"94","author":[{"given":"Qiang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haote","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4091-1936","authenticated-orcid":false,"given":"Hetian","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajian","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.tice.2025.102817_bib1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.preteyeres.2015.08.001","article-title":"The progress in understanding and treatment of diabetic retinopathy","volume":"51","author":"Stitt","year":"2016","journal-title":"Prog. Retin Eye Res"},{"key":"10.1016\/j.tice.2025.102817_bib2","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.2147\/DDDT.S383101","article-title":"Progress and challenges of anti-VEGF agents and their sustained-release strategies for retinal angiogenesis","volume":"16","author":"Xu","year":"2022","journal-title":"Drug Des. Dev. Ther."},{"key":"10.1016\/j.tice.2025.102817_bib3","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1007\/s00125-023-05940-5","article-title":"What else can we do to prevent diabetic retinopathy?","volume":"66","author":"Simo","year":"2023","journal-title":"Diabetologia"},{"key":"10.1016\/j.tice.2025.102817_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.jare.2024.07.006","article-title":"Exploitation of enhanced prime editing for blocking aberrant angiogenesis","author":"Huang","year":"2024","journal-title":"J. Adv. Res"},{"key":"10.1016\/j.tice.2025.102817_bib5","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/j.cmet.2024.04.013","article-title":"Diabetic retinopathy is a ceramidopathy reversible by anti-ceramide immunotherapy","volume":"36","author":"Dorweiler","year":"2024","journal-title":"Cell Metab."},{"key":"10.1016\/j.tice.2025.102817_bib6","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2320034121","article-title":"Modulation of diabetes-related retinal pathophysiology by PTX3","volume":"121","author":"Pathak","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.tice.2025.102817_bib7","doi-asserted-by":"crossref","first-page":"736","DOI":"10.2337\/db19-0713","article-title":"PI3Kdelta as a novel therapeutic target in pathological angiogenesis","volume":"69","author":"Wu","year":"2020","journal-title":"Diabetes"},{"key":"10.1016\/j.tice.2025.102817_bib8","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1089\/hum.2022.079","article-title":"H: genome editing of Pik3cd impedes abnormal retinal angiogenesis","volume":"34","author":"Wu","year":"2023","journal-title":"Hum. gene Ther."},{"key":"10.1016\/j.tice.2025.102817_bib9","article-title":"Nationwide trends and incidence of blindness in patients with diabetic retinopathy identified using an age-period-cohort analysis","author":"Lee","year":"2024","journal-title":"Eye (Lond. )"},{"key":"10.1016\/j.tice.2025.102817_bib10","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0165-6147(00)01676-X","article-title":"FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition","volume":"22","author":"Cross","year":"2001","journal-title":"Trends Pharm. Sci."},{"key":"10.1016\/j.tice.2025.102817_bib11","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.2147\/OPTH.S248812","article-title":"Budu: vitreous and serum concentrations of vascular endothelial growth factor and platelet-derived growth factor in proliferative diabetic retinopathy","volume":"14","author":"Muhiddin","year":"2020","journal-title":"Clin. Ophthalmol."},{"key":"10.1016\/j.tice.2025.102817_bib12","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1126\/science.6823562","article-title":"Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid","volume":"219","author":"Senger","year":"1983","journal-title":"Science"},{"key":"10.1016\/j.tice.2025.102817_bib13","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.93751","article-title":"Diabetic retinopathy: current understanding, mechanisms, and treatment strategies","volume":"2","author":"Duh","year":"2017","journal-title":"JCI Insight"},{"key":"10.1016\/j.tice.2025.102817_bib14","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1056\/NEJMoa1007374","article-title":"Group B-RC: Efficacy of intravitreal bevacizumab for stage 3+\u2009retinopathy of prematurity","volume":"364","author":"Mintz-Hittner","year":"2011","journal-title":"N. Engl. J. Med"},{"key":"10.1016\/j.tice.2025.102817_bib15","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1016\/S0140-6736(13)61501-9","article-title":"investigators Is: Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial","volume":"382","author":"Chakravarthy","year":"2013","journal-title":"Lancet"},{"key":"10.1016\/j.tice.2025.102817_bib16","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1038\/s41433-018-0021-7","article-title":"Clinical pharmacoloy of intravitreal anti-VEGF drugs","volume":"32","author":"Fogli","year":"2018","journal-title":"Eye"},{"key":"10.1016\/j.tice.2025.102817_bib17","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1001\/jamaophthalmol.2024.3283","article-title":"Initial therapy of panretinal photocoagulation vs anti-VEGF injection for proliferative diabetic retinopathy","volume":"142","author":"Alsoudi","year":"2024","journal-title":"JAMA Ophthalmol."},{"key":"10.1016\/j.tice.2025.102817_bib18","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1136\/bjophthalmol-2013-304670","article-title":"Predictive factors for non-response to intravitreal ranibizumab treatment in age-related macular degeneration","volume":"98","author":"Suzuki","year":"2014","journal-title":"Br. J. Ophthalmol."},{"key":"10.1016\/j.tice.2025.102817_bib19","doi-asserted-by":"crossref","first-page":"4774","DOI":"10.1158\/0008-5472.CAN-07-6307","article-title":"BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy","volume":"68","author":"Hilberg","year":"2008","journal-title":"Cancer Res"},{"key":"10.1016\/j.tice.2025.102817_bib20","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1124\/jpet.113.208223","article-title":"Antifibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosis","volume":"349","author":"Wollin","year":"2014","journal-title":"J. Pharm. Exp. Ther."},{"key":"10.1016\/j.tice.2025.102817_bib21","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1177\/1753465815579365","article-title":"Nintedanib in the treatment of idiopathic pulmonary fibrosis","volume":"9","author":"Mazzei","year":"2015","journal-title":"Ther. Adv. Respir. Dis."},{"key":"10.1016\/j.tice.2025.102817_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.115403","article-title":"Nintedanib inhibits normal human vitreous-induced epithelial-mesenchymal transition in human retinal pigment epithelial cells","volume":"166","author":"Yin","year":"2023","journal-title":"Biomed. Pharm."},{"key":"10.1016\/j.tice.2025.102817_bib23","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1183\/09031936.00174914","article-title":"Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis","volume":"45","author":"Wollin","year":"2015","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.tice.2025.102817_bib24","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1056\/NEJMoa1402584","article-title":"Investigators IT: Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis","volume":"370","author":"Richeldi","year":"2014","journal-title":"N. Engl. J. Med"},{"key":"10.1016\/j.tice.2025.102817_bib25","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1183\/09059180.00008913","article-title":"Therapeutic options targeting angiogenesis in nonsmall cell lung cancer","volume":"23","author":"Crino","year":"2014","journal-title":"Eur. Respir. Rev."},{"key":"10.1016\/j.tice.2025.102817_bib26","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jconrel.2015.01.001","article-title":"Light-responsive nanoparticle depot to control release of a small molecule angiogenesis inhibitor in the posterior segment of the eye","volume":"200","author":"Huu","year":"2015","journal-title":"J. Control Release"},{"key":"10.1016\/j.tice.2025.102817_bib27","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s10456-017-9543-z","article-title":"Effects of nintedanib on the microvascular architecture in a lung fibrosis model","volume":"20","author":"Ackermann","year":"2017","journal-title":"Angiogenesis"},{"key":"10.1016\/j.tice.2025.102817_bib28","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.omtn.2023.08.001","article-title":"Leverage of nuclease-deficient CasX for preventing pathological angiogenesis","volume":"33","author":"Han","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"10.1016\/j.tice.2025.102817_bib29","article-title":"Axl is essential for in-vitro angiogenesis induced by vitreous from patients with proliferative diabetic retinopathy","volume":"8","author":"Wu","year":"2021","journal-title":"Front Med (Lausanne)"},{"key":"10.1016\/j.tice.2025.102817_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.preteyeres.2024.101271","article-title":"Resilience to diabetic retinopathy","volume":"101","author":"Serikbaeva","year":"2024","journal-title":"Prog. Retin Eye Res"},{"key":"10.1016\/j.tice.2025.102817_bib31","doi-asserted-by":"crossref","DOI":"10.3390\/cells10051069","article-title":"Cytokine levels in human vitreous in proliferative diabetic retinopathy","volume":"10","author":"Loporchio","year":"2021","journal-title":"Cells"},{"key":"10.1016\/j.tice.2025.102817_bib32","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nprot.2007.30","article-title":"In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro","volume":"2","author":"Liang","year":"2007","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.tice.2025.102817_bib33","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0002-9440(10)64363-5","article-title":"The alpha(1)beta(1) and alpha(2)beta(1) integrins provide critical support for vascular endothelial growth factor signaling, endothelial cell migration, and tumor angiogenesis","volume":"160","author":"Senger","year":"2002","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.tice.2025.102817_bib34","doi-asserted-by":"crossref","DOI":"10.1016\/j.labinv.2023.100228","article-title":"Role of stromal fibroblast-induced WNT7A associated with cancer cell migration through AKT\/CLDN1 signaling axis in oral squamous cell carcinoma","author":"Kayamori","year":"2023","journal-title":"Lab Invest"},{"key":"10.1016\/j.tice.2025.102817_bib35","doi-asserted-by":"crossref","first-page":"3488","DOI":"10.1091\/mbc.e04-11-1029","article-title":"Cathepsin B regulates the intrinsic angiogenic threshold of endothelial cells","volume":"16","author":"Im","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.tice.2025.102817_bib36","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/nm0195-27","article-title":"Angiogenesis in cancer, vascular, rheumatoid and other disease","volume":"1","author":"Folkman","year":"1995","journal-title":"Nat. Med"},{"key":"10.1016\/j.tice.2025.102817_bib37","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1161\/01.RES.0000259593.07661.1e","article-title":"Endothelial cell migration during angiogenesis","volume":"100","author":"Lamalice","year":"2007","journal-title":"Circ. Res"},{"key":"10.1016\/j.tice.2025.102817_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.preteyeres.2019.03.002","article-title":"Human vitreous in proliferative diabetic retinopathy: characterization and translational implications","volume":"72","author":"Nawaz","year":"2019","journal-title":"Prog. Retin Eye Res"},{"key":"10.1016\/j.tice.2025.102817_bib39","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1167\/iovs.16-20537","article-title":"Editing VEGFR2 blocks VEGF-induced activation of Akt and tube formation","volume":"58","author":"Huang","year":"2017","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.tice.2025.102817_bib40","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1161\/01.RES.86.1.4","article-title":"Akt takes center stage in angiogenesis signaling","volume":"86","author":"Dimmeler","year":"2000","journal-title":"Circ. Res"},{"key":"10.1016\/j.tice.2025.102817_bib41","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/IAE.0000000000002789","article-title":"Brimo DDSGSG: phase 2 study of the safety and efficacy of brimonidine drug delivery system (Brimo Dds) generation 1 in patients with geographic atrophy secondary to age-related macular degeneration","volume":"41","author":"Kuppermann","year":"2021","journal-title":"Retina"},{"key":"10.1016\/j.tice.2025.102817_bib42","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1038\/s41433-021-01616-9","article-title":"Ranibizumab Biosimilar (Razumab) vs Innovator Ranibizumab (Lucentis) in neovascular age-related macular degeneration (n-AMD)- efficacy and safety (BIRA study)","volume":"36","author":"Sharma","year":"2022","journal-title":"Eye (Lond. )"},{"key":"10.1016\/j.tice.2025.102817_bib43","doi-asserted-by":"crossref","DOI":"10.1155\/2023\/7355039","article-title":"BIBF1120 protects against diabetic retinopathy through neovascularization-related molecules and the MAPK signaling pathway","volume":"2023","author":"Cao","year":"2023","journal-title":"J. Ophthalmol."}],"container-title":["Tissue and Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0040816625000977?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0040816625000977?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T14:04:12Z","timestamp":1741615452000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0040816625000977"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":43,"alternative-id":["S0040816625000977"],"URL":"https:\/\/doi.org\/10.1016\/j.tice.2025.102817","relation":{},"ISSN":["0040-8166"],"issn-type":[{"value":"0040-8166","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Nintedanib abrogates patient vitreous-induced Akt activation and tube formation of human retinal microvascular endothelial cells","name":"articletitle","label":"Article Title"},{"value":"Tissue and Cell","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tice.2025.102817","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"102817"}}