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Gene delivery of calreticulin anti-angiogenic domain attenuates the development of choroidal neovascularization in rats
Citation
Bee, Y-S and Tu, L and Sheu, S-J and Lin, H-C and Tang, J-H and Wang, J-H and Prea, SM and Dusting, GJ and Wu, D-C and Zhong, J and Bui, BV and Tai, M-H and Liu, G-S, Gene delivery of calreticulin anti-angiogenic domain attenuates the development of choroidal neovascularization in rats, Human Gene Therapy, 28, (5) pp. 403-414. ISSN 1043-0342 (2017) [Refereed Article]
Copyright Statement
Copyright 2017 by Mary Ann Liebert
Abstract
Choroidal 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.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | choroidal neovascularization, gene delivery, CAD, adenovirus |
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Medical biotechnology |
| Research Field: | Gene and molecular therapy |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Liu, G-S (Associate Professor Guei-Sheung Liu) |
| ID Code: | 123375 |
| Year Published: | 2017 |
| Web of Science® Times Cited: | 1 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2018-01-03 |
| Last Modified: | 2018-03-07 |
| Downloads: | 0 |
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