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

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 and Liu, G-S ORCID: 0000-0003-3379-724X 2017 , 'Gene delivery of calreticulin anti-angiogenic domain attenuates the development of choroidal neovascularization in rats' , Human Gene Therapy, vol. 28, no. 5 , pp. 403-414 , doi: 10.1089/hum.2016.035.

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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 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 Type: Article
Authors/Creators: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
Keywords: choroidal neovascularization, gene delivery, CAD, adenovirus
Journal or Publication Title: Human Gene Therapy
Publisher: Mary Ann Liebert Inc Publ
ISSN: 1043-0342
DOI / ID Number: 10.1089/hum.2016.035
Copyright Information:

Copyright 2017 by Mary Ann Liebert

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