{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:59:51Z","timestamp":1790823591678,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR2240, Cu47\/4\u20102, Cu 47\/6\u20101, Cu 47\/9\u20101 (CC) (BO4489\/1\u20101, BO4489\/1\u20102)"],"award-info":[{"award-number":["FOR2240, Cu47\/4\u20102, Cu 47\/6\u20101, Cu 47\/9\u20101 (CC) (BO4489\/1\u20101, BO4489\/1\u20102)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009983","name":"Center for Molecular Medicine Cologne, University of Cologne","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009983","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82560203"],"award-info":[{"award-number":["82560203"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Exper Ophthalmology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>To investigate, for the first time, whether an unconjugated VEGF\u2010A antisense oligonucleotide (ASO) can inhibit corneal neovascularisation and improve graft survival in a murine high\u2010risk corneal transplantation model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A suture\u2010induced corneal neovascularisation model was established in BALB\/c mice, followed by high\u2010risk corneal transplantation using C57BL\/6 donor corneas. A VEGF\u2010A RNase H\u2013recruiting ASO (gapmer) was delivered via subconjunctival injection, topical eye drops, or ex\u00a0vivo preincubation of donor corneas. Blood vessels (BVs) and lymphatic vessels (LVs) were quantified by immunohistochemistry, and\n                      <jats:italic>Vegfa<\/jats:italic>\n                      mRNA expression was measured by qPCR. Immune cell profiles in draining lymph nodes (dLNs), focusing on regulatory T cells (Tregs) and dendritic cells (DCs), were analysed by flow cytometry. Graft survival was monitored for 8\u2009weeks using Kaplan\u2013Meier analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Subconjunctival and topical VEGF\u2010A ASO administration significantly suppressed corneal hemangiogenesis and lymphangiogenesis (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Subconjunctival injection also induced regression of established vessels (BVs \u221221.76%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0039; LVs \u221249.75%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0110). Graft survival improved significantly after subconjunctival treatment (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0438) and donor cornea preincubation (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0148). Flow cytometry showed increased Treg frequency in dLNs following subconjunctival ASO administration (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0293). Preincubation of donor corneas markedly reduced\n                      <jats:italic>Vegfa<\/jats:italic>\n                      mRNA levels (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>VEGF\u2010A\u2013targeting ASO effectively inhibits corneal neovascularisation and improves graft survival in high\u2010risk transplantation. Local and ex\u00a0vivo VEGF\u2010A inhibition using ASO represents a promising therapeutic strategy for controlling ocular neovascularisation and enhancing corneal transplant outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ceo.70159","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T07:53:41Z","timestamp":1788940421000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>VEGF<\/scp>\n                    \u2010A Antisense Oligonucleotide Therapy Inhibits Corneal Neovascularisation and Enhances Graft Survival in Murine High\u2010Risk Corneal Transplantation"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5757-2398","authenticated-orcid":false,"given":"Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology University of Cologne, Faculty of Medicine and University Hospital Cologne  Cologne Germany"},{"name":"Department of Ophthalmology, Hebei Eye Hospital Hebei Key Laboratory of Ophthalmology  Xingtai Hebei China"},{"name":"Department of Ophthalmology Affiliated Hospital of Guizhou Medical University, Guizhou Medical University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Weile","sequence":"additional","affiliation":[{"name":"BioInnovation Institute  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1044-6722","authenticated-orcid":false,"given":"Christoph","family":"Ullmer","sequence":"additional","affiliation":[{"name":"Roche Pharma Research &amp; Early Development Roche Innovation Center Basel, F. Hoffmann\u2010La Roche Ltd  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2522-5743","authenticated-orcid":false,"given":"Sascha","family":"Fauser","sequence":"additional","affiliation":[{"name":"Roche Pharma Research &amp; Early Development Roche Innovation Center Basel, F. Hoffmann\u2010La Roche Ltd  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5691-8289","authenticated-orcid":false,"given":"Felix","family":"Bock","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Cologne, Faculty of Medicine and University Hospital Cologne  Cologne Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC) University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1958-411X","authenticated-orcid":false,"given":"Claus","family":"Cursiefen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Cologne, Faculty of Medicine and University Hospital Cologne  Cologne Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC) University of Cologne  Cologne Germany"},{"name":"CECAD Cluster of Excellence University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001281"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2010.01.039"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2019.07.001"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-200304000-00021"},{"issue":"2","key":"e_1_2_9_6_1","first-page":"455","article-title":"Vascular Endothelial Growth Factor (VEGF)\u2014Key Factor in Normal and Pathological Angiogenesis","volume":"59","author":"Melincovici C. 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