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タイトル: | High‐Density Lipoprotein Engineering for Eye‐Drop Treatment of Age‐Related Macular Degeneration |
著者: | Fukuda, Ryosuke Mahmuda, Nargis Kasirawat, Sawangrat Kawakami, Ryo Shima, Rumina Mizukami, Yu Shibukawa, Shiori Tada, Yuki Kawanishi, Fumitake Ogura, Masatsune Matsuki, Kota Nagai, Yoshinori Nakano, Eri Suda, Kenji https://orcid.org/0000-0003-1636-0898 (unconfirmed) Tsujikawa, Akitaka Murakami, Tatsuya |
著者名の別形: | 中野, 絵梨 須田, 謙史 辻川, 明孝 村上, 達也 |
キーワード: | absorption enhancer age-related macular degeneration antiangiogenic activity anti-inflammatory activity high-density lipoproteins neovasculature-targeting |
発行日: | Nov-2023 |
出版者: | Wiley |
誌名: | Advanced Therapeutics |
巻: | 6 |
号: | 11 |
論文番号: | 2300186 |
抄録: | Eye-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. |
著作権等: | © 2023 The Authors. Advanced Therapeutics published by Wiley-VCH GmbH This 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. |
URI: | http://hdl.handle.net/2433/287121 |
DOI(出版社版): | 10.1002/adtp.202300186 |
出現コレクション: | 学術雑誌掲載論文等 |
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