{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:24:47Z","timestamp":1785216287965,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,3,31]],"date-time":"2018-03-31T00:00:00Z","timestamp":1522454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Variable new antigen receptor domain (vNAR) antibodies are novel, naturally occurring antibodies that can be isolated from na\u00efve, immune or synthetic shark libraries. These molecules are very interesting to the biotechnology and pharmaceutical industries because of their unique characteristics related to size and tissue penetrability. There have been some approved anti-angiogenic therapies for ophthalmic conditions, not related to vNAR. This includes biologics and chimeric proteins that neutralize vascular endothelial growth factor (VEGF)165, which are injected intravitreal, causing discomfort and increasing the possibility of infection. In this paper, we present a vNAR antibody against human recombinant VEGF165 (rhVEGF165) that was isolated from an immunized Heterodontus francisci shark. A vNAR called V13, neutralizes VEGF165 cytokine starting at 75 \u03bcg\/mL in an in vitro assay based on co-culture of normal human dermal fibroblasts (NHDFs) and green fluorescence protein (GFP)-labeled human umbilical vein endothelial cells (HUVECs) cells. In the oxygen-induced retinopathy model in C57BL\/6:Hsd mice, we demonstrate an endothelial cell count decrease. Further, we demonstrate the intraocular penetration after topical administration of 0.1 \u03bcg\/mL of vNAR V13 by its detection in aqueous humor in New Zealand rabbits with healthy eyes after 3 h of application. These findings demonstrate the potential of topical application of vNAR V13 as a possible new drug candidate for vascular eye diseases.<\/jats:p>","DOI":"10.3390\/md16040113","type":"journal-article","created":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T12:32:20Z","timestamp":1522672340000},"page":"113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Intraocular Penetration of a vNAR: In Vivo and In Vitro VEGF165 Neutralization"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0540-0287","authenticated-orcid":false,"given":"Tanya","family":"Camacho-Villegas","sequence":"first","affiliation":[{"name":"CONACYT-Medical and Pharmaceutical Biotechnology, Centro de Investigaci\u00f3n y Asistencia en Tecnolog\u00eda y Dise\u00f1o del Estado de Jalisco (CIATEJ), Guadalajara, Jalisco, C.P. 44270, Mexico"},{"name":"Biomedical Innovation Department, Centro de Investigaci\u00f3n Cient\u00edfica y Educaci\u00f3n Superior de Ensenada, (CICESE), Ensenada, Baja California, C.P. 22860, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Mata-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Research and Development Department, Laboratorios Silanes S.A. de C.V., Ciudad de M\u00e9xico, C. P. 03100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2102-6018","authenticated-orcid":false,"given":"Walter","family":"Garc\u00eda-Ubbelohd","sequence":"additional","affiliation":[{"name":"Research and Development Department, Laboratorios Silanes S.A. de C.V., Ciudad de M\u00e9xico, C. P. 03100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"N\u00fa\u00f1ez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Research and Development Department, Laboratorios Silanes S.A. de C.V., Ciudad de M\u00e9xico, C. P. 03100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Elosua","sequence":"additional","affiliation":[{"name":"Research and Development Department, Teracl\u00f3n IDF S.L., Calle de Santiago Grisol\u00eda, Tres Cantos, 28020 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Paniagua-Solis","sequence":"additional","affiliation":[{"name":"Research and Development Department, Laboratorios Silanes S.A. de C.V., Ciudad de M\u00e9xico, C. P. 03100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4022-7405","authenticated-orcid":false,"given":"Alexei","family":"Licea-Navarro","sequence":"additional","affiliation":[{"name":"Biomedical Innovation Department, Centro de Investigaci\u00f3n Cient\u00edfica y Educaci\u00f3n Superior de Ensenada, (CICESE), Ensenada, Baja California, C.P. 22860, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1177\/2042018813512360","article-title":"Anti-vascular endothelial growth factor therapy for diabetic macular edema","volume":"4","author":"Boyer","year":"2013","journal-title":"Ther. Adv. Endocrinol. 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