{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:24:47Z","timestamp":1785295487989,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T00:00:00Z","timestamp":1617926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Health &amp; Welfare, Republic of Korea","award":["HI17C2273"],"award-info":[{"award-number":["HI17C2273"]}]},{"name":"the Korean Government","award":["2017R1A5A1015366 and 2020R1F1A1075725"],"award-info":[{"award-number":["2017R1A5A1015366 and 2020R1F1A1075725"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>It has been shown previously that a novel tetrapeptide, Arg-Leu-Tyr-Glu (RLYE), derived from human plasminogen inhibits vascular endothelial growth factor (VEGF)-induced angiogenesis, suppresses choroidal neovascularization in mice by an inhibition of VEGF receptor-2 (VEGFR-2) specific signaling pathway. In this study, we report that a modified tetrapeptide (Ac-RLYE) showed improved anti-choroidal neovascularization (CNV) efficacy in a number of animal models of neovascular age-related macular degeneration (AMD) which include rat, rabbit, and minipig. The preventive and therapeutic in vivo efficacy of Ac-RLYE via following intravitreal administration was determined to be either similar or superior to that of ranibizumab and aflibercept. Assessment of the intraocular pharmacokinetic and toxicokinetic properties of Ac-RLYE in rabbits demonstrated that it rapidly reached the retina with minimal systemic exposure after a single intravitreal dose, and it did not accumulate in plasma during repetitive dosing (bi-weekly for 14 weeks). Our results suggested that Ac-RLYE has a great potential for an alternative therapeutics for neovascular (wet) AMD. Since the amino acids in human VEGFR-2 targeted by Ac-RLYE are conserved among the animals employed in this study, the therapeutic efficacies of Ac-RLYE evaluated in those animals are predicted to be observed in human patients suffering from retinal degenerative diseases.<\/jats:p>","DOI":"10.3390\/ijms22083893","type":"journal-article","created":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T10:05:21Z","timestamp":1617962721000},"page":"3893","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Therapeutic Efficacy of a Novel Acetylated Tetrapeptide in Animal Models of Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"22","author":[{"given":"Hye Cheong","family":"Koo","sequence":"first","affiliation":[{"name":"Avixgen Inc., Seoul 06649, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Yong","family":"Baek","sequence":"additional","affiliation":[{"name":"Avixgen Inc., Seoul 06649, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Sup","family":"Choi","sequence":"additional","affiliation":[{"name":"Avixgen Inc., Seoul 06649, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8326-7768","authenticated-orcid":false,"given":"Young-Myeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon 24341, Gangwon-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bokyung","family":"Sung","sequence":"additional","affiliation":[{"name":"Avixgen Inc., Seoul 06649, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Avixgen Inc., Seoul 06649, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Gyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Avixgen Inc., Seoul 06649, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Chang","family":"You","sequence":"additional","affiliation":[{"name":"Avixgen Inc., Seoul 06649, Korea"},{"name":"National Research Laboratory for Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea, Seoul 06591, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1056\/NEJMoa054481","article-title":"MARINA Study Group. 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