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Gene delivery of calreticulin anti-angiogenic domain attenuates the development of choroidal neovascularization in rats


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

DOI: doi:10.1089/hum.2016.035


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

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