{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:22:51Z","timestamp":1790648571269,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T00:00:00Z","timestamp":1595289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY028996"],"award-info":[{"award-number":["R01EY028996"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R44EY025470"],"award-info":[{"award-number":["R44EY025470"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL101200"],"award-info":[{"award-number":["R01HL101200"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["F32CA210482"],"award-info":[{"award-number":["F32CA210482"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Persistent inflammation is a complication associated with many ocular diseases. Changes in ocular vessels can amplify disease responses and contribute to vision loss by influencing the delivery of leukocytes to the eye, vascular leakage, and perfusion. Here, we report the anti-inflammatory activity for AXT107, a non-RGD, 20-mer \u03b1v\u03b23 and \u03b15\u03b21 integrin-binding peptide that blocks vascular endothelial growth factor (VEGF)-signaling and activates tyrosine kinase with immunoglobulin and EGF-like domains 2 (Tie2) using the normally inhibitory ligand angiopoietin 2 (Ang2). Tumor necrosis factor \u03b1 (TNF\u03b1), a central inflammation mediator, induces Ang2 release from endothelial cells to enhance its stimulation of inflammation and vascular leakage. AXT107 resolves TNF\u03b1-induced vascular inflammation in endothelial cells by converting the endogenously released Ang2 into an agonist of Tie2 signaling, thereby disrupting both the synergism between TNF\u03b1 and Ang2 while also preventing inhibitor of nuclear factor-\u03baB \u03b1 (I\u03baB\u03b1) degradation directly through Tie2 signaling. This recovery of I\u03baB\u03b1 prevents nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB) nuclear localization, thereby blocking NF-\u03baB-induced inflammatory responses, including the production of VCAM-1 and ICAM-1, leukostasis, and vascular leakage in cell and mouse models. AXT107 also decreased the levels of pro-inflammatory TNF receptor 1 (TNFR1) without affecting levels of the more protective TNFR2. These data suggest that AXT107 may provide multiple benefits in the treatment of retinal\/choroidal and other vascular diseases by suppressing inflammation and promoting vascular stabilization.<\/jats:p>","DOI":"10.3390\/ijms21145142","type":"journal-article","created":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T06:38:55Z","timestamp":1595313535000},"page":"5142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Suppression of Ocular Vascular Inflammation through Peptide-Mediated Activation of Angiopoietin-Tie2 Signaling"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0602-3011","authenticated-orcid":false,"given":"Adam C.","family":"Mirando","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Lima e Silva","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zenny","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Campochiaro","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niranjan B.","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"AsclepiX Therapeutics, Inc., Baltimore, MD 21211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6706-9235","authenticated-orcid":false,"given":"Aleksander S.","family":"Popel","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1080\/03007995.2018.1512961","article-title":"The burden of non-infectious intraocular inflammatory eye diseases: A systematic literature review","volume":"34","author":"Rice","year":"2018","journal-title":"Curr. 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