{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:13:26Z","timestamp":1773296006882,"version":"3.50.1"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T00:00:00Z","timestamp":1617926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Tumor necrosis factor (TNF)\u03b1 is an inflammatory cytokine likely to be involved in the process of corneal inflammation and neovascularization. In the present study we evaluate the role of the two receptors, TNF-receptor (TNF-R)p55 and TNF-Rp75, in the mouse model of suture-induced corneal neovascularization and lymphangiogenesis. Corneal neovascularization and lymphangiogenesis were induced by three 11\u20130 intrastromal corneal sutures in wild-type (WT) C57BL\/6J mice and TNF-Rp55-deficient (<jats:italic>TNF-Rp55d<\/jats:italic>) and TNF-Rp75-deficient (<jats:italic>TNF-Rp75d<\/jats:italic>) mice. The mRNA expression of VEGF-A, VEGF-C, Lyve-1 and TNF\u03b1 and its receptors was quantified by qPCR. The area covered with blood- or lymphatic vessels, respectively, was analyzed by immunohistochemistry of corneal flatmounts. Expression and localization of TNF\u03b1 and its receptors was assessed by immunohistochemistry of sagittal sections and Western Blot. Both receptors are expressed in the murine cornea and are not differentially regulated by the genetic alteration. Both <jats:italic>TNF-Rp55d<\/jats:italic> and <jats:italic>TNF-Rp75d<\/jats:italic> mice showed a decrease in vascularized area compared to wild-type mice 14 days after suture treatment. After 21 days there were no differences detectable between the groups. The number of VEGF-A-expressing macrophages did not differ when comparing WT to <jats:italic>TNF-Rp55d<\/jats:italic> and <jats:italic>TNF-Rp75d<\/jats:italic>. The mRNA expression of lymphangiogenic markers VEGF-C or LYVE-1 does not increase after suture in all 3 groups and lymphangiogenesis showed a delayed effect only for <jats:italic>TNF-Rp75d<\/jats:italic>. TNF\u03b1 mRNA and protein expression increased after suture treatment but showed no difference between the three groups. In the suture-induced mouse model, TNF\u03b1 and its ligands TNF-Rp55 and TNF-Rp75 do not play a significant role in the pathogenesis of neovascularisation and lymphangiogenesis.<\/jats:p>","DOI":"10.1371\/journal.pone.0245143","type":"journal-article","created":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T17:31:48Z","timestamp":1617989508000},"page":"e0245143","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Effects of TNF\u03b1 receptor TNF-Rp55- or TNF-Rp75- deficiency on corneal neovascularization and lymphangiogenesis in the mouse"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8095-0254","authenticated-orcid":true,"given":"Anna-Karina B.","family":"Maier","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine","family":"Reichhart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Gonnermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Kociok","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline I.","family":"Riechardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enken","family":"Gundlach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olaf","family":"Strau\u00df","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia M.","family":"Joussen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,4,9]]},"reference":[{"issue":"4","key":"pone.0245143.ref001","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1097\/01.ico.0000183485.85636.ff","article-title":"Time course of angiogenesis and lymphangiogenesis after brief corneal inflammation","volume":"25","author":"C Cursiefen","year":"2006","journal-title":"Cornea"},{"issue":"7","key":"pone.0245143.ref002","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1167\/iovs.06-1083","article-title":"Endogenous TNFalpha suppression of neovascularization in corneal stroma in mice","volume":"48","author":"S Fujita","year":"2007","journal-title":"Investigative ophthalmology & visual science"},{"issue":"4","key":"pone.0245143.ref003","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/00055735-200108000-00002","article-title":"Corneal neovascularization","volume":"12","author":"JH Chang","year":"2001","journal-title":"Current opinion in ophthalmology"},{"issue":"4","key":"pone.0245143.ref004","first-page":"292","article-title":"[Angiogenesis and lymphangiogenesis in the cornea. 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