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Title: High‐Density Lipoprotein Engineering for Eye‐Drop Treatment of Age‐Related Macular Degeneration
Authors: 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  kyouindb  KAKEN_id  orcid (unconfirmed)
Tsujikawa, Akitaka  kyouindb  KAKEN_id
Murakami, Tatsuya
Author's alias: 中野, 絵梨
須田, 謙史
辻川, 明孝
村上, 達也
Keywords: absorption enhancer
age-related macular degeneration
antiangiogenic activity
anti-inflammatory activity
high-density lipoproteins
Issue Date: Nov-2023
Publisher: Wiley
Journal title: Advanced Therapeutics
Volume: 6
Issue: 11
Thesis number: 2300186
Abstract: 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.
Rights: © 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.
DOI(Published Version): 10.1002/adtp.202300186
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