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Gene delivery of calreticulin anti-angiogenic domain attenuates the development of choroidal neovascularization in rats
journal contribution
posted on 2023-05-19, 14:37 authored by Bee, Y-S, Tu, L, Sheu, S-J, Lin, H-C, Tang, J-H, Wang, J-H, Prea, SM, Dusting, GJ, Wu, D-C, Zhong, J, Bui, BV, Tai, M-H, Guei-Sheung LiuGuei-Sheung LiuChoroidal neovascularization (CNV) is a common pathological feature in neovascular age-related macular degeneration, which is the leading cause of vision loss among elderly populations in developed countries. This study evaluated the effect of a novel endogenous inhibitor of angiogenesis, calreticulin anti-angiogenic domain (CAD), subconjunctivally delivered by an adenoviral vector (Ad-CAD) in a rat model of laser-induced CNV. CAD was expressed in Ad-CAD-infected cells and inhibited the angiogenic activity in human umbilical vein endothelial cells in vitro. CAD expression was also found in various ocular tissues after in vivo subconjunctival Ad-CAD injection. Via bioluminescence imaging it is shown that a single subconjunctival injection of Ad-luciferase induced the expression of the transgene in the injected eyes within 24 h, which lasted for at least 112 days. Forty-two days after subconjunctival injection of Ad-CAD, retinal structure and function were unaffected, as measured using optical coherence tomography and electroretinography, respectively. After laser injury, subconjunctival Ad-CAD gene delivery significantly inhibited CNV lesions as measured via choroid flat-mounts (51% reduction at 21 days; p < 0.001), as well as by fundus fluorescein angiography (19.3%, 28.2%, 31%, and 27.5% reductions at days 21, 28, 35, and 42, respectively; p < 0.05) in rats. The data suggest that subconjunctival Ad-CAD gene therapy could effectively inhibit laser-induced CNV and might be an attractive therapeutic approach for the management of choroidal neovascularization.
History
Publication title
Human Gene TherapyVolume
28Issue
5Pagination
403-414ISSN
1043-0342Department/School
Menzies Institute for Medical ResearchPublisher
Mary Ann Liebert Inc PublPlace of publication
2 Madison Avenue, Larchmont, USA, Ny, 10538Rights statement
Copyright 2017 by Mary Ann LiebertRepository Status
- Restricted