{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T13:14:08Z","timestamp":1775999648012,"version":"3.50.1"},"reference-count":33,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ophthalmic Res"],"published-print":{"date-parts":[[2023]]},"abstract":"<b><i>Introduction:<\/i><\/b> The purpose of this study was to determine if conjunctival lymphangiogenesis can be induced using adenoviral delivery of vascular endothelial growth factor C (VEGF-C). <b><i>Methods:<\/i><\/b> Seventeen New Zealand white rabbits received a subconjunctival injection containing 3.5 \u00d7 10<sup>7<\/sup> plaque-forming units of an adenoviral vector containing the gene-encoding VEGF-C (Ad-VEGF-C). The contralateral eye was used for control experiment (the same volume of either saline or an empty vector). After 2 weeks, the animals were examined with trypan blue conjunctival lymphangiography, and the eyes were harvested for histology and immunohistochemistry (podoplanin and CD31). <b><i>Results:<\/i><\/b> Trypan blue conjunctival lymphangiography revealed significantly more extensive conjunctival vessel network in the Ad-VEGF-C group compared with control: 1.35 \u00b1 0.67 versus 0.28 \u00b1 0.17 vessel length\/analysed area (<i>p<\/i> = &lt;0.0001). This finding was confirmed with immunohistochemistry, where a significant increase in the number of lymphatic vessels was found compared to control; 34 \u00b1 9 per mm<sup>2<\/sup> versus 13 \u00b1 8 per mm<sup>2<\/sup> (<i>p<\/i> = 0.0019). Furthermore, there was a significant increase in lymphatic cross-sectional area; 32,500 \u00b1 7,900 \u00b5m<sup>2<\/sup> per mm<sup>2<\/sup> versus 17,600 \u00b1 9,700 \u00b5m<sup>2<\/sup> per mm<sup>2<\/sup> (<i>p<\/i> = 0.0149). Quantification of blood vessels revealed no significant difference in blood vessel density between Ad-VEGF-C and control; 19 \u00b1 9 per mm<sup>2<\/sup> versus 14 \u00b1 8 per mm<sup>2<\/sup> (<i>p<\/i> = 0.1971). There was no significant difference in total blood vessel area; 13,200 \u00b1 7,600 \u00b5m<sup>2<\/sup> per mm<sup>2<\/sup> versus 7,100 \u00b1 3,000 \u00b5m<sup>2<\/sup> per mm<sup>2<\/sup> (<i>p<\/i> = 0.0715). Eyes treated with an adenoviral vector (VEGF-C or empty vector) responded with a reactive cellular response, predominantly lymphocytes, towards the vector. <b><i>Conclusion:<\/i><\/b> The study demonstrates the feasibility of inducing conjunctival lymphangiogenesis with a single subconjunctival injection of Ad-VEGF-C. Future studies will explore how this can be used with a therapeutic purpose. <\/jats:p>","DOI":"10.1159\/000533427","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T21:01:27Z","timestamp":1691614887000},"page":"1128-1138","source":"Crossref","is-referenced-by-count":3,"title":["Local Adenoviral Delivery of Vascular Endothelial Growth Factor C Induces Lymphangiogenesis in the Conjunctiva in Rabbits"],"prefix":"10.1159","volume":"66","author":[{"given":"Dusan","family":"Rasic","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Wirenfeldt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne Louise","family":"Askou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Corydon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niklas","family":"Telinius","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2023,8,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903180"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.13534"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2009.06.004"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0179com"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.039"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2022.02.019"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.3776"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-015-9469-2"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038\/nm1689"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1172\/JCI75395"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65021-3"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.63.10.16"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8712-2_19"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00487-6"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2020.05.014"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-018-0035-6"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0000000000002736"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1002\/med.21496"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjps.2020.05.009"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.14670\/HH-18-300"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1038\/s41433-020-1031-9"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1038\/eye.1993.108"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.05.076"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1549-8719.2000.tb00127.x"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00471"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100559"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124850"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.09.012"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1001\/archophthalmol.2012.293"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-200404000-00013"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2011.05.025"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2010.01.032"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-0156"}],"container-title":["Ophthalmic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/ore\/article-pdf\/66\/1\/1128\/3997049\/000533427.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/ore\/article-pdf\/66\/1\/1128\/3997049\/000533427.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:36:32Z","timestamp":1745422592000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000533427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12,20]]}},"URL":"https:\/\/doi.org\/10.1159\/000533427","archive":["Portico"],"relation":{},"ISSN":["0030-3747","1423-0259"],"issn-type":[{"value":"0030-3747","type":"print"},{"value":"1423-0259","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023]]}}}