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dc.contributor.authorFukuda, Ryosukeen
dc.contributor.authorMahmuda, Nargisen
dc.contributor.authorKasirawat, Sawangraten
dc.contributor.authorKawakami, Ryoen
dc.contributor.authorShima, Ruminaen
dc.contributor.authorMizukami, Yuen
dc.contributor.authorShibukawa, Shiorien
dc.contributor.authorTada, Yukien
dc.contributor.authorKawanishi, Fumitakeen
dc.contributor.authorOgura, Masatsuneen
dc.contributor.authorMatsuki, Kotaen
dc.contributor.authorNagai, Yoshinorien
dc.contributor.authorNakano, Erien
dc.contributor.authorSuda, Kenjien
dc.contributor.authorTsujikawa, Akitakaen
dc.contributor.authorMurakami, Tatsuyaen
dc.contributor.alternative中野, 絵梨ja
dc.contributor.alternative須田, 謙史ja
dc.contributor.alternative辻川, 明孝ja
dc.contributor.alternative村上, 達也ja
dc.date.accessioned2024-02-28T09:00:36Z-
dc.date.available2024-02-28T09:00:36Z-
dc.date.issued2023-11-
dc.identifier.urihttp://hdl.handle.net/2433/287121-
dc.description.abstractEye-drop treatments of age-related macular degeneration (AMD) are desirable; however, no clinically approved eye drop has been reported to date. This study aim to evaluate the therapeutic activity of eye-drop instillation of a high-density lipoprotein (HDL) variant bearing a cell-penetrating peptide and neovasculature-targeted peptide (AsnGlyArg [NGR] peptide) in a mouse model at a dose of 0.6–0.85 µg protein/eye drop. The results reveal that the activity of the abovementioned variant was >10-fold higher than that of the previous variant lacking an NGR peptide. In addition, the anti-inflammatory activity, cholesterol-efflux capacity, and antiangiogenic activity of reconstituted HDL are significantly augmented by the attachment of these two peptides. The mechanism underlying this dramatic improvement is likely the expression of CD13, an NGR peptide receptor, on the cornea and conjunctiva in mice. CD13 mRNA/protein expression is also detected in cultured human corneal and conjunctival cells. These results demonstrate that NGR peptide is an unprecedented class of an absorption enhancer on the eye surface. Thus, HDL engineering is a potential strategy for developing eye drops to treat neovascular AMD by enhancing the ocular surface absorption and HDL functionalities.en
dc.language.isoeng-
dc.publisherWileyen
dc.rights© 2023 The Authors. Advanced Therapeutics published by Wiley-VCH GmbHen
dc.rightsThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/-
dc.subjectabsorption enhanceren
dc.subjectage-related macular degenerationen
dc.subjectantiangiogenic activityen
dc.subjectanti-inflammatory activityen
dc.subjecthigh-density lipoproteinsen
dc.subjectneovasculature-targetingen
dc.titleHigh‐Density Lipoprotein Engineering for Eye‐Drop Treatment of Age‐Related Macular Degenerationen
dc.typejournal article-
dc.type.niitypeJournal Article-
dc.identifier.jtitleAdvanced Therapeuticsen
dc.identifier.volume6-
dc.identifier.issue11-
dc.relation.doi10.1002/adtp.202300186-
dc.textversionpublisher-
dc.identifier.artnum2300186-
dcterms.accessRightsopen access-
datacite.awardNumber20K18378-
datacite.awardNumber18K18460-
datacite.awardNumber21H03821-
datacite.awardNumber.urihttps://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20K18378/-
datacite.awardNumber.urihttps://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18K18460/-
datacite.awardNumber.urihttps://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21H03821/-
dc.identifier.eissn2366-3987-
jpcoar.funderName日本学術振興会ja
jpcoar.funderName日本学術振興会ja
jpcoar.funderName日本学術振興会ja
jpcoar.awardTitle血管親和性生体ナノ材料を用いた加齢黄斑変性の点眼治療の開発ja
jpcoar.awardTitle血中に存在するリポタンパク質の異所利用:加齢黄斑変性の点眼治療法開発に向けてja
jpcoar.awardTitle治療用ナノ粒子の創製:リポタンパク質の構造と機能に着目した眼難治疾患治療戦略ja
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